创伤脓毒症中Th17细胞/CD4~+CD25~+Foxp3~+调节性T细胞失衡的研究
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摘要
【目的】研究创伤脓毒症过程中Th17细胞与CD4+CD25+Foxp3+调节性T细胞平衡及相关细胞因子的变化情况,以及糖皮质激素/糖皮质激素受体对脓毒症Th17/Treg的调控作用,丰富对创伤脓毒症后免疫功能紊乱发生机制的认识,并为探索调节创伤脓毒症后免疫功能紊乱的措施提供新的治疗靶点。
【方法】临床研究：收集2010年9月至2011年1月间我院创伤外科收治的35例创伤患者(其中13例并发脓毒症、22例未并发脓毒症)以及9例健康志愿者进行临床研究。主要研究内容包括：(1)分离外周血淋巴细胞后流式细胞技术检测Th17细胞、CD4+CD25+Foxp3+调节性T细胞比例；(2)实时荧光定量PCR(real-time qPCR)检测Th17细胞特异性转录因子RORγt mRNA水平表达、CD4+CD25+Foxp3+调节性T细胞特异性转录因子Foxp3 mRNA水平表达；(3)分离外周血清检测C反应蛋白和相关细胞因子(IL-4,IL-6,IL-10,IL-17,IL-23, INF-γ,TGF-β)含量,结合临床资料加以分析。
动物实验：利用Balb/C小鼠建立盲肠结扎穿孔脓毒症模型。将实验动物分为脓毒症组、干预组、假手术组及对照组,干预组在脓毒症组的基础上使用糖皮质激素受体阻滞剂RU486干预；观察指标包括(1)脓毒症过程中不同时相小鼠脾脏淋巴细胞Th17细胞和Treg细胞比例；(2)脾脏细胞特征性的转录因子RORγt和Foxp3的mRNA水平表达；(3)血清细胞因子含量(IL-2.4.6.10.17.INF-γ.TGF-p等)；(4)脓毒症后迟发型超敏反应程度。
【结果】临床研究：创伤脓毒症组住院天数和病死率均高于严重创伤组(P<0.05)；严重创伤组外周血Th17细胞比例较健康对照组稍高但差异无统计学意义,创伤脓毒症组外周血Th17细胞比例明显高于其它两组(P<0.01)；外周血Treg细胞比例,严重创伤组及创伤脓毒症组均较健康对照组高(P<0.01),严重创伤组与创伤脓毒症组间差异无统计学意义；外周血Th17/Treg细胞比值创伤脓毒症组较其它两组高(P<0.01),严重创伤组与健康对照组比较略低(P<0.05)；创伤脓毒症组的RORyt mRNA水平表达均高于其它两组(P<0.01),健康对照组与严重创伤组间差异无统计学意义；Foxp3 mRNA水平表达,创伤脓毒症组及严重创伤组均较健康对照组高(P<0.01),其中创伤脓毒症组较严重创伤组稍高(P<0.05)；创伤脓毒症组血清TGF-β,IL-6及IL-23含量均明显高于健康对照组(P<0.01)；严重创伤组血清TGF-β和IL-6含量明显高于健康对照组,而血清IL-23含量与健康对照组相比差异无统计学意义；创伤脓毒症组与严重创伤组比较血清TGF-β含量无明显差异,而血清IL-6,IL-23含量明显高于后者(P<0.01)；创伤脓毒症组外周血IL-17含量明显高于严重创伤组及健康对照组(P<0.01),其余两组差异无统计学意义；创伤脓毒症组及严重创伤组外周血IL-10含量明显高于健康对照组(P<0.01),创伤脓毒症组与严重创伤组比较IL-10含量前者高于后者(P<0.01)；脓毒症组及创伤组血清CRP含量均明显高于对照组(P<0.01),脓毒症组略高于创伤组(P<0.05)；血清INF-γ含量创伤组低于对照组(P<0.05),脓毒症组更低(P<0.01)；血清IL-4含量创伤脓毒症组较其它两组略高(P<0.05),其余两组差异无统计学意义。
动物实验：建模后第1天脓毒症组、RU干预组及假手术组Th17细胞比例与对照组比较均升高(P<0.01)；随后脓毒症组与RU干预组Th17细胞比例继续上升,第3天达到顶峰,假手术组较前无明显变化；第7天脓毒症组及RU干预组Th17细胞比例下降,与假手术组间差异变小(P<0.05)；第14天各组Th17细胞比例差异无统计学意义。脓毒症组与RU干预组间比较差异无统计学意义。建模后第1天,脓毒症组和RU干预组Treg细胞比例均较对照组及假手术组明显升高(P<0.01),第3天时略有下降,第3天后不断增高；脓毒症组和RU干预组之间比较,脓毒症组Treg细胞比例较RU干预组高,在1d,3d时相P<0.05；假手术组与对照组比较,比例稍高,但差异无统计学意义。脓毒症组和RU干预组第3天Th17/Treg比值较正常升高(P<0.01),而第14天较对照组低,但差异无统计学意义(P>0.05)；两组间比较RU干预组比值较高但各时相均无统计学差异。建模后1天,脓毒症组、RU干预组脾脏细胞RORyt mRNA水平表达均较假手术组和正常对照组明显升高(P<0.01),且在第3天达到峰值；随后下降,第7d和14d与假手术组无明显差异。脓毒症组与干预组比较,干预组在第1天,第3天更高(P<0.05)。建模后脓毒症组,干预组及假手术组各时点Foxp3 mRNA水平表达均较对照组高(P<0.01)；三组间比较,第1天、第14天脓毒症组及RU干预组均明显高于假手术组(P<0.01),第3天、第7天略有下降与假手术组差异变小；脓毒症组与干预组比较,前者略高于后者(P<0.05)。
脓毒症组及RU干预组在第3天血清IL-17含量明显高于假手术组及对照组(P<0.01),此后回落,第7d、14d各组间差异无统计学意义；脓毒症组与干预组比较干预组第3天稍高于脓毒症组(P<0.05)。脓毒症组、干预组及假手术组IL-10含量均升高,脓毒症组及干预组均明显高于假手术组(P<0.01)；其中第3天脓毒症组及干预组都有少许下降,但仍高于假手术组(P<0.01)。建模后脓毒症组,干预组及假手术组血清IL-10均高于对照组,其中脓毒症组及干预组高于假手术组,脓毒症组与干预组比较差异无统计学意义。脓毒症组和RU干预组在第1天,第3天血清IL-6含量明显高于假手术组和对照组(P<0.01),两组间比较RU干预组在第3天时相高于脓毒症组(P<0.01)。脓毒症组和RU干预组IL-2含量较对照组及假手术组高(P<0.05),脓毒症组及RU干预组在第3天时相较其它时相略低(P<0.05),脓毒症组及干预组两组间比较差异无统计学意义。血清INF-γ含量脓毒症组,干预组及假手术组均高于对照组(P<0.05),第1天干预组较脓毒症组高,而后两者差异无统计学意义。血清IL-4含量ELISA检测结果显示,各组间差异无统计学意义。DTH实验结果表明,假手术组和对照组间差异无统计学意义；脓毒症组及RU干预组DTH反应较对照组及假手术组弱(P<0.01),同时脓毒症组与RU干预组比较其反应更弱(P<0.05)。
【结论】临床研究和动物实验研究均表明Thl7细胞参与创伤脓毒症中的炎症反应,Treg细胞参与脓毒症中的抗炎反应并维持迁延的免疫抑制状态；脓毒症时发生Th17/Treg失衡,是脓毒症后免疫功能紊乱的重要机制。GC/GR参与引起脓毒症中Th17细胞/Treg细胞失衡,拮抗GR可部分逆转脓毒症后免疫抑制。
Objective:To investigate the imbalance between Th17 cell and CD4+CD25+Foxp3+ regulatory T cell (Treg), the expression of related cytokines and the possible mechanism during posttraumatic sepsis process. To further explore the pathogenesis of disturbed adaptive immune response during posttraumatic sepsis.
Methods:clinical reseach:35 cases of severe traumatic patients (13 cases with posttraumatic sepsis while 22 cases without) and 9 cases of healthy volunteers were enrolled in this study. The main research contents include separating peripheral blood lymphocyte to detect the percentage of Th17 cell and Treg cell by Flow, the expression of RORyt mRNA and Foxp3 mRNA by qPCR, at the same time the related cytokines in serum such as CRP, IL-4, IL-6,IL-10, IL-17, IL-23,INF-γ, TGF-βwere tested by ELISA and all the data were analysed combined with the clinical data.
Animal experiment:52 cases of male Balb/c were separate into control group (4 cases), sham group(16 cases), CLP group(16 cases) and RU group(16 cases) randomly and underwent relevant treatments. Investigated the percentage of Th17 cell and Treg cell, the expression of RORγt mRNA and Foxp3 mRNA in spleen, and the related cytokines in serum such as IL-2,IL-4, IL-6, IL-10, IL-17, INF-γand TGF-β. Meanwhile, the DTH reaction was measured to evaluate the T cell response.
Results:clinical reseach:The hospital stay and case fatality rate in sepsis group is higher than those in trauma group (P<0.05).The proportion of Th17 cells and mRNA expression of transcription factor RORyt in sepsis group was found to be significantly higher than that in healthy control or trauma group (P<0.01). The proportion of Treg cells and the mRNA expression of the transcription factor Foxp3 were significantly increased in sepsis group and trauma group (P<0.05). while there is no significant difierence between these two groups (P>0.05). Serum levels of Thl7 inducing cytokine such as IL-6, IL-23 and IL-17 were significantly elevated in sepsis group than that in trauma group or healthy control group(P<0.05), while cytokine such as TGF-βand IL-10 were found higher in sepsis and trauma group than that in healthy control group (P<0.01). Serum levels of CRP and IL-4 in trauma group and sepsis group was higher(P<0.05) than those in control group while levels of INF-γwas lower (P<0.05). Animal experiment:Proportion of Thl7 cell in CLP group, RU group and sham group was found increased from the fitst day compared with control group (P<0.01), then CLP and RU group continued to increase to day 3, then decreased, the difference between these two group was not significant (P>0.05), while the mRNA expression of transcription factor RORγt and the serum levels of Th17 inducing cytokine such as IL-6, IL-17 had a similar variation tendency. Proportion of Treg cell in CLP and RU group was found in a sustainable growth with a only a slightly reduction in the 3rd day. Between these two groups, the proportion of Treg cell was higher in CLP group (P< 0.05). the mRNA expression of Treg cell transcription factor Foxp3 and the serum levels of Treg cell related cytokines such as TGF-P, IL-2, IL-10 had a similar variation tendency. Serum levels of INF-y and IL-4 were found no significant difference among all groups. The DTH test showed that the response of mice in sham group and control group has no significant difference, while RU group and CLP group had significant lower response (P<0.01). between these two group, the CLP group had the lower response (P<0.05).
Conclusion:Th17 cells involve in the inflammation during posttraumatic sepsis. Treg cells play an anti-inflammatory role during posttraumatic sepsis and maintain a deferment immunosuppression state. Th17/Treg imbalance occurs after sepsis, is the important mechanism of immune disorders. GC/GR participation may cause Thl7/Treg cell imbalance during posttraumatic sepsis. Moderate antagonist glucocorticoids function may in some extent reverse imbalance of Thl7/Treg cell, and reverse excessive deferment immunosuppression. Those may contribute to the state of the original infection status thoroughly clearance and prevent the occurrence of secondary infection, improve the prognosis.
【方法】临床研究：收集2010年9月至2011年1月间我院创伤外科收治的35例创伤患者(其中13例并发脓毒症、22例未并发脓毒症)以及9例健康志愿者进行临床研究。主要研究内容包括：(1)分离外周血淋巴细胞后流式细胞技术检测Th17细胞、CD4+CD25+Foxp3+调节性T细胞比例；(2)实时荧光定量PCR(real-time qPCR)检测Th17细胞特异性转录因子RORγt mRNA水平表达、CD4+CD25+Foxp3+调节性T细胞特异性转录因子Foxp3 mRNA水平表达；(3)分离外周血清检测C反应蛋白和相关细胞因子(IL-4,IL-6,IL-10,IL-17,IL-23, INF-γ,TGF-β)含量,结合临床资料加以分析。
动物实验：利用Balb/C小鼠建立盲肠结扎穿孔脓毒症模型。将实验动物分为脓毒症组、干预组、假手术组及对照组,干预组在脓毒症组的基础上使用糖皮质激素受体阻滞剂RU486干预；观察指标包括(1)脓毒症过程中不同时相小鼠脾脏淋巴细胞Th17细胞和Treg细胞比例；(2)脾脏细胞特征性的转录因子RORγt和Foxp3的mRNA水平表达；(3)血清细胞因子含量(IL-2.4.6.10.17.INF-γ.TGF-p等)；(4)脓毒症后迟发型超敏反应程度。
【结果】临床研究：创伤脓毒症组住院天数和病死率均高于严重创伤组(P<0.05)；严重创伤组外周血Th17细胞比例较健康对照组稍高但差异无统计学意义,创伤脓毒症组外周血Th17细胞比例明显高于其它两组(P<0.01)；外周血Treg细胞比例,严重创伤组及创伤脓毒症组均较健康对照组高(P<0.01),严重创伤组与创伤脓毒症组间差异无统计学意义；外周血Th17/Treg细胞比值创伤脓毒症组较其它两组高(P<0.01),严重创伤组与健康对照组比较略低(P<0.05)；创伤脓毒症组的RORyt mRNA水平表达均高于其它两组(P<0.01),健康对照组与严重创伤组间差异无统计学意义；Foxp3 mRNA水平表达,创伤脓毒症组及严重创伤组均较健康对照组高(P<0.01),其中创伤脓毒症组较严重创伤组稍高(P<0.05)；创伤脓毒症组血清TGF-β,IL-6及IL-23含量均明显高于健康对照组(P<0.01)；严重创伤组血清TGF-β和IL-6含量明显高于健康对照组,而血清IL-23含量与健康对照组相比差异无统计学意义；创伤脓毒症组与严重创伤组比较血清TGF-β含量无明显差异,而血清IL-6,IL-23含量明显高于后者(P<0.01)；创伤脓毒症组外周血IL-17含量明显高于严重创伤组及健康对照组(P<0.01),其余两组差异无统计学意义；创伤脓毒症组及严重创伤组外周血IL-10含量明显高于健康对照组(P<0.01),创伤脓毒症组与严重创伤组比较IL-10含量前者高于后者(P<0.01)；脓毒症组及创伤组血清CRP含量均明显高于对照组(P<0.01),脓毒症组略高于创伤组(P<0.05)；血清INF-γ含量创伤组低于对照组(P<0.05),脓毒症组更低(P<0.01)；血清IL-4含量创伤脓毒症组较其它两组略高(P<0.05),其余两组差异无统计学意义。
动物实验：建模后第1天脓毒症组、RU干预组及假手术组Th17细胞比例与对照组比较均升高(P<0.01)；随后脓毒症组与RU干预组Th17细胞比例继续上升,第3天达到顶峰,假手术组较前无明显变化；第7天脓毒症组及RU干预组Th17细胞比例下降,与假手术组间差异变小(P<0.05)；第14天各组Th17细胞比例差异无统计学意义。脓毒症组与RU干预组间比较差异无统计学意义。建模后第1天,脓毒症组和RU干预组Treg细胞比例均较对照组及假手术组明显升高(P<0.01),第3天时略有下降,第3天后不断增高；脓毒症组和RU干预组之间比较,脓毒症组Treg细胞比例较RU干预组高,在1d,3d时相P<0.05；假手术组与对照组比较,比例稍高,但差异无统计学意义。脓毒症组和RU干预组第3天Th17/Treg比值较正常升高(P<0.01),而第14天较对照组低,但差异无统计学意义(P>0.05)；两组间比较RU干预组比值较高但各时相均无统计学差异。建模后1天,脓毒症组、RU干预组脾脏细胞RORyt mRNA水平表达均较假手术组和正常对照组明显升高(P<0.01),且在第3天达到峰值；随后下降,第7d和14d与假手术组无明显差异。脓毒症组与干预组比较,干预组在第1天,第3天更高(P<0.05)。建模后脓毒症组,干预组及假手术组各时点Foxp3 mRNA水平表达均较对照组高(P<0.01)；三组间比较,第1天、第14天脓毒症组及RU干预组均明显高于假手术组(P<0.01),第3天、第7天略有下降与假手术组差异变小；脓毒症组与干预组比较,前者略高于后者(P<0.05)。
脓毒症组及RU干预组在第3天血清IL-17含量明显高于假手术组及对照组(P<0.01),此后回落,第7d、14d各组间差异无统计学意义；脓毒症组与干预组比较干预组第3天稍高于脓毒症组(P<0.05)。脓毒症组、干预组及假手术组IL-10含量均升高,脓毒症组及干预组均明显高于假手术组(P<0.01)；其中第3天脓毒症组及干预组都有少许下降,但仍高于假手术组(P<0.01)。建模后脓毒症组,干预组及假手术组血清IL-10均高于对照组,其中脓毒症组及干预组高于假手术组,脓毒症组与干预组比较差异无统计学意义。脓毒症组和RU干预组在第1天,第3天血清IL-6含量明显高于假手术组和对照组(P<0.01),两组间比较RU干预组在第3天时相高于脓毒症组(P<0.01)。脓毒症组和RU干预组IL-2含量较对照组及假手术组高(P<0.05),脓毒症组及RU干预组在第3天时相较其它时相略低(P<0.05),脓毒症组及干预组两组间比较差异无统计学意义。血清INF-γ含量脓毒症组,干预组及假手术组均高于对照组(P<0.05),第1天干预组较脓毒症组高,而后两者差异无统计学意义。血清IL-4含量ELISA检测结果显示,各组间差异无统计学意义。DTH实验结果表明,假手术组和对照组间差异无统计学意义；脓毒症组及RU干预组DTH反应较对照组及假手术组弱(P<0.01),同时脓毒症组与RU干预组比较其反应更弱(P<0.05)。
【结论】临床研究和动物实验研究均表明Thl7细胞参与创伤脓毒症中的炎症反应,Treg细胞参与脓毒症中的抗炎反应并维持迁延的免疫抑制状态；脓毒症时发生Th17/Treg失衡,是脓毒症后免疫功能紊乱的重要机制。GC/GR参与引起脓毒症中Th17细胞/Treg细胞失衡,拮抗GR可部分逆转脓毒症后免疫抑制。
Objective:To investigate the imbalance between Th17 cell and CD4+CD25+Foxp3+ regulatory T cell (Treg), the expression of related cytokines and the possible mechanism during posttraumatic sepsis process. To further explore the pathogenesis of disturbed adaptive immune response during posttraumatic sepsis.
Methods:clinical reseach:35 cases of severe traumatic patients (13 cases with posttraumatic sepsis while 22 cases without) and 9 cases of healthy volunteers were enrolled in this study. The main research contents include separating peripheral blood lymphocyte to detect the percentage of Th17 cell and Treg cell by Flow, the expression of RORyt mRNA and Foxp3 mRNA by qPCR, at the same time the related cytokines in serum such as CRP, IL-4, IL-6,IL-10, IL-17, IL-23,INF-γ, TGF-βwere tested by ELISA and all the data were analysed combined with the clinical data.
Animal experiment:52 cases of male Balb/c were separate into control group (4 cases), sham group(16 cases), CLP group(16 cases) and RU group(16 cases) randomly and underwent relevant treatments. Investigated the percentage of Th17 cell and Treg cell, the expression of RORγt mRNA and Foxp3 mRNA in spleen, and the related cytokines in serum such as IL-2,IL-4, IL-6, IL-10, IL-17, INF-γand TGF-β. Meanwhile, the DTH reaction was measured to evaluate the T cell response.
Results:clinical reseach:The hospital stay and case fatality rate in sepsis group is higher than those in trauma group (P<0.05).The proportion of Th17 cells and mRNA expression of transcription factor RORyt in sepsis group was found to be significantly higher than that in healthy control or trauma group (P<0.01). The proportion of Treg cells and the mRNA expression of the transcription factor Foxp3 were significantly increased in sepsis group and trauma group (P<0.05). while there is no significant difierence between these two groups (P>0.05). Serum levels of Thl7 inducing cytokine such as IL-6, IL-23 and IL-17 were significantly elevated in sepsis group than that in trauma group or healthy control group(P<0.05), while cytokine such as TGF-βand IL-10 were found higher in sepsis and trauma group than that in healthy control group (P<0.01). Serum levels of CRP and IL-4 in trauma group and sepsis group was higher(P<0.05) than those in control group while levels of INF-γwas lower (P<0.05). Animal experiment:Proportion of Thl7 cell in CLP group, RU group and sham group was found increased from the fitst day compared with control group (P<0.01), then CLP and RU group continued to increase to day 3, then decreased, the difference between these two group was not significant (P>0.05), while the mRNA expression of transcription factor RORγt and the serum levels of Th17 inducing cytokine such as IL-6, IL-17 had a similar variation tendency. Proportion of Treg cell in CLP and RU group was found in a sustainable growth with a only a slightly reduction in the 3rd day. Between these two groups, the proportion of Treg cell was higher in CLP group (P< 0.05). the mRNA expression of Treg cell transcription factor Foxp3 and the serum levels of Treg cell related cytokines such as TGF-P, IL-2, IL-10 had a similar variation tendency. Serum levels of INF-y and IL-4 were found no significant difference among all groups. The DTH test showed that the response of mice in sham group and control group has no significant difference, while RU group and CLP group had significant lower response (P<0.01). between these two group, the CLP group had the lower response (P<0.05).
Conclusion:Th17 cells involve in the inflammation during posttraumatic sepsis. Treg cells play an anti-inflammatory role during posttraumatic sepsis and maintain a deferment immunosuppression state. Th17/Treg imbalance occurs after sepsis, is the important mechanism of immune disorders. GC/GR participation may cause Thl7/Treg cell imbalance during posttraumatic sepsis. Moderate antagonist glucocorticoids function may in some extent reverse imbalance of Thl7/Treg cell, and reverse excessive deferment immunosuppression. Those may contribute to the state of the original infection status thoroughly clearance and prevent the occurrence of secondary infection, improve the prognosis.
引文
[1]Levy MM, Fink MP,Marshall JC, et al.2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference [J]. Crit Care Med,2003, 31(4):1250-6. Review.
[2]林洪远,盛志勇.我们需要一个更清晰的脓毒症概念和标准——介绍和评析2001年华盛顿国际脓毒症定义会议[J].中华外科杂志,2004,42(14)：836-838.
[3]Singh S, Evans TW. Organ dysfunction during sepsis [J]. Intensive Care Med, 2006,32(3):349-360.
[4]盛志勇,姚咏明.脓毒症研究的现状与展望[J].解放军医学杂志,1999,24(2)：79-82.
[5]Angus DC, Linde-Zwirble WT, Lidicker J, et al.Epidemiology of severe sepsis in the United States:analysis of incidence, outcome, and associated costs of care [J]. Crit Care Med.2001 Jul;29(7):1303-10.
[6]Brun-Buisson C, Roudot-Thoraval F, Girou E, et al.The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis [J]. Intensive Care Med.2003 Sep;29(9):1464-71.Epub 2003 Jul 10.
[7]姚咏明,柴家科,林洪远.现代脓毒症理论与实践[S].第1版.北京：科学出版社,2005,1-7.
[8]王正国.脓毒症研究概况[J].中华创伤杂志,2003,19(1)：5-8.
[9]李春盛.关于脓毒症的几个问题[J].中国危重病急救医学.2002,14(6)：323-328.
[10]Nagler-Anderson C, Bhan AK, Podolsky DK, el al. Control freaks:immune regulatory cells [J]. Nat Immunol.2004 Feb;5(2):119-22.
[11]Annunziato F, Cosmi L, Santarlasci V, Phenotypic and functional features of human Th17 cells [J]. J Exp Med.2007 Aug 6;204(8):1849-61. Epub 2007 Jul 16.
[12]Fazilleau N, Mark L, McHeyzer-Williams LJ, Follicular helper T cells:lineage and location [J]. Immunity.2009 Mar 20;30(3):324-35.
[13]Liang SC, Tan XY,Luxenberg DP,Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides[J]. J Exp Med.2006 Oct 2;203(10):2271-9. Epub 2006 Sep 18.
[14]Harris TJ, Grosso JF,Yen HR,Cutting edge:An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity [J].J Immunol.2007 Oct1;179(7):4313-7.
[15]Komiyama Y, Nakae S,Matsuki T, et al.IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].J Immunol.2006 Jul 1;177(1):566-73.
[16]Rao DA, Eid RE,Qin L, et al.Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection [J]. J Exp Med.2008 Dec 22;205(13):3145-58. Epub 2008 Dec 15.
[17]Paradowska A,Masliniski W,Grzybowska-Kowalczyk A,et al.The function of interleukin 17 in the pathogenesis of rheumatoid arthritis [J].Arch Immunol Ther Exp (Warsz).2007 Sep-Oct;55(5):329-34.
[18]Emamaullee JA, Davis J, Merani S, et al.Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice [J]. Diabetes.2009 Jun;58(6):1302-11. Epub 2009 Mar 16.
[19]Seene T,Kaasik P,Pehme A,et al.The effect of glucocorticoids on the myosin heavy chain isoforms turnover in skeletal muscle [J]. J Steroid Biochem Mol Biol.2003 Aug;86(2):201-6.
[20]Wang L, Luo GJ, Wang JJ, et al.Dexamethasone stimulates proteasome- and Calcium-dependent proteolysis in cultured L6 myocytes [J]. Shock.1998 Oct;10(4): 298-306.
[21]Bledsoe RK,Montana VG, Stanley TB. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition [J]. Cell,2002,110(1):93-105.
[22]Vegiopoulos A,Herzig S.Glucocorticoids, metabolism and metabolic diseases.Mol Cell Endocrinol[J].2007 Sep 15;275(1-2):43-61.Epub 2007 Jun 2.
[23]De Bosscher K, Beck IM, Haegeman G.Classic glucocorticoids versus non-steroidal glucocorticoid receptor modulators:survival of the fittest regulator of the immune system?Brain Behav Immun[J].2010 Oct;24(7):1035-42. Epub 2010 Jun 25.
[24]Heuer JG, Zhang T, Zhao J, Adoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis[J].J Immunol.2005 Jun 1;174(11):7141-6.
[25]唐朝晖,余彦,白祥军等,严重多发伤患者外周血CD4+CD25mgh调节性T细胞的变化及意义[J].中华创伤杂志,2008,24(2)：92-95.
[26]Mangan PR,Harrington LE,O'Quinn DB,Transforming growth factor-beta induces development of the T(H)17 lineage[J]. Nature.2006 May 11;441(7090):231-4. Epub 2006 Apr 30.
[27]Volpe E, Servant N, Zollinger R, A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating humanT(H)-17 responses[J]. Nat Immunol.2008 Jun;9(6):650-7. Epub 2008 May 4.
[28]Korn T, Oukka M, Kuchroo V, Th17 cells:effector T cells with inflammatory properties [J]. Semin Immunol.2007 Dec;19(6):362-71.Epub 2007 Nov 26.
[29]Komiyama Y, Nakae S, Matsuki T, IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis[J]. J Immunol.2006 Jul 1;177(1):566-73.
[30]Happel KI,Dubin PJ,Zheng M, Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae[J]. J Exp Med.2005 Sep 19;202(6):761-9. Epub 2005 Sep 12.
[31]Sergio L. Zanotti-Cavazzoni, Roy D. Animal Models of Sepsis[J]. Goldfarb, Crit Care Clin 25 (2009) 703-719
[32]Yao Z, Painter SL, Fanslow WC, Human IL-17:a novel cytokine derived from T cells. J Immunol[J].1995 Dec 15;155(12):5483-6.
[33]Fossiez F, Djossou O, Chomarat P, T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J]. J Exp Med.1996 Jun 1;183(6):2593-603.
[34]姚咏明.免疫功能紊乱在脓毒症发病中的作用及意义[J].中国危重病急救医学,2007,19(3)：138-141.
[35]Zhou L, Lopes JE, Chong MM, et al.TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function [J]. Nature.2008 May 8;453(7192):236-40. Epub 2008 Mar 26.
[36]Veldhoen M, Hocking RJ, Atkins CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells [J]. Immunity.2006 Feb;24(2):179-89.
[37]Laurence A, Tato CM, Davidson TS, et al. Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[38]Meakins JL, Pietsch JB, Bubenick O, et al. Delayed hypersensitivity:indicator of acquired failure of host defenses in sepsis and trauma [J]. Ann Surg.1977 sep; 186(3):241-50.
[39]Moore FA, Sauaia A,Moore EE, et al.Postinjury multiple organ failure:a bimodal phenomenon [J]. J Trauma 1996;40:501-510;dicussion,510-502
[40]Mannick JA, Rodrick ML, Lederer JA.The immunologic response to injury [J].J Am Coll Surg.2001 Sep;193(3):237-44.
[1]Korn T, Bettelli E, Oukka M, IL-17 and Th17 Cells [J]. Annu Rev Immunol.2009;27:485-517.
[2]Hue S,Ahern P,Buonocore S, et al.Interleukin-23 drives innate and T cell-mediated intestinal inflammation [J].J Exp Med.2006 Oct 30;203(11):2473-83.
[3]Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease [J]. Gut.2003 Jan;52(1):65-70.
[4]Csiszar A, Ungvari Z, Koller A,et al.Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries [J].FASEB J.2003 Jun;17(9): 1183-5. Epub 2003 Apr 22.
[5]Komiyama Y, Nakae S, Matsuki T, IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].J Immunol.2006 Jul 1;177(1):566-73.
[6]Paradowska A, Masliniski W, Grzybowska-Kowalczyk A, The function of interleukin 17 in the pathogenesis of rheumatoid arthritis [J]. Arch Immunol Ther Exp (Warsz).2007 Sep-Oct;55(5):329-34.
[7]Jones CE, Chan K. Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells [J]. Am J Respir Cell Mol Biol.2002 Jun;26(6):748-53.
[8]Zhang Z, Zheng M, Bindas J, Critical role of IL-17 receptor signaling in acute TNBS-induced colitis [J]. Inflamm Bowel Dis.2006 May;12(5):382-8.
[9]Rao DA, Eid RE,Qin L, Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection [J]. J Exp Med.2008 Dec 22;205(13):3145-58. Epub 2008 Dec 15.
[10]Emamaullee JA, Davis J, Merani S, Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice [J]. Diabetes.2009 Jun;58(6):1302-11. Epub 2009 Mar 16.
[11]Mosmann TR, Coffman RL. TH1 and TH2 cells:different patterns of lymphokine secretion lead to different functional properties [J]. Annu Rev Immunol.1989;7:145-73.
[12]Annunziato F,Cosmi L,Santarlasci V,Phenotypic and functional features of human Th17 cells [J].J Exp Med.2007 Aug 6;204(8):1849-61. Epub 2007 Jul 16.
[13]Fazilleau N, Mark L, McHeyzer-Williams LJ, Follicular helper T cells:lineage and location [J]. Immunity.2009 Mar 20;30(3):324-35.
[14]Harrington LE, Hatton RD, Mangan PR, Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J]. Nat Immunol.2005 Nov;6(11):1123-32. Epub 2005 Oct 2.
[15]Liang SC, Tan XY, Luxenberg DP, Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides [J]. J Exp Med.2006 Oct 2;203(10):2271-9. Epub 2006 Sep 18.
[16]Cua DJ, Sherlock J, Chen Y, Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain [J]. Nature.2003 Feb 13;421(6924):744-8.
[17]Li MO, Wan YY,Flavell RA. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Thl-and Th17-cell differentiation [J].Immunity.2007 May;26(5):579-91. Epub 2007 May 3.
[18]Mangan PR, Harrington LE, O'Quinn DB,Transforming growth factor-beta induces development of the T(H) 17 lineage [J]. Nature.2006 May 11;441(7090):231-4. Epub 2006 Apr 30.
[19]Volpe E,Servant N,Zollinger R,A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses [J]. Nat Immunol.2008 Jun;9(6):650-7. Epub 2008 May 4.
[20]Langrish CL, Chen Y, Blumenschein WM, IL-23 drives a pathogenic T cell population that induces autoimmune inflammation [J]. J Exp Med.2005 Jan 17;201(2):233-40.
[21]Korn T, Oukka M, Kuchroo V,Th17 cells:effector T cells with inflammatory properties [J]. Semin Immunol.2007 Dec;19(6):362-71.Epub 2007 Nov 26.
[22]Bettelli E, Carrier Y, Gao W,Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006 May 11;441(7090):235-8.Epub 2006 Apr 30.
[23]Wilson NJ, Boniface K, Chan JR,Development, cytokine profile and function of human interleukin 17-producing helper T cells [J]. Nat Immunol.2007 Sep;8(9):950-7. Epub 2007 Aug 5.
[24]Schraml BU, Hildner K,Ise W,The AP-1 transcription factor Batf controls T(H)17 differentiation [J]. Nature.2009 Jul 16;460(7253):405-9. Epub 2009 Jul 5.
[25]Harris TJ, Grosso JF, Yen HR, Cutting edge:An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity [J]. J Immunol.2007 Oct 1;179(7):4313-7.
[26]McGeachy MJ, Chen Y, Tato CM, The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo [J]. Nat Immunol.2009 Mar; 10(3):314-24. Epub 2009 Feb 1.
[27]Nurieva R, Yang XO,Martinez G, Essential autocrine regulation by IL-21 in the generation of inflammatory T cells [J]. Nature.2007 Jul 26;448(7152):480-3. Epub 2007 Jun 20.
[28]Korn T,Bettelli E,Gao W, IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells [J]. Nature.2007 Jul 26;448(7152):484-7. Epub 2007 Jun 20.
[29]Zhou L,Ivanov II,Spolski R,IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways [J]. Nat Immunol.2007 Sep;8(9):967-74. Epub 2007 Jun 20.
[30]Szabo SJ, Sullivan BM, Peng SL, Molecular mechanisms regulating Thl immune responses [J]. Annu Rev Immunol.2003;21:713-58. Epub 2001 Dec 19.
[31]Glimcher LH, Murphy KM. Lineage commitment in the immune system:the T helper lymphocyte grows up [J]. Genes Dev.2000 Jul 15; 14(14):1693-711.
[32]Park H, Li Z,Yang XO,Chang SH, A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 [J]. Nat Immunol.2005 Nov;6(11):1133-41.Epub 2005 Oct 2.
[33]Sundrud MS, Koralov SB,Feuerer M,Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response [J]. Science.2009 Jun 5;324(5932):1334-8.
[34]Rouvier E,Luciani MF,Mattei MG,CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene [J]. J Immunol.1993 Jun 15;150(12):5445-56.
[35]Lee J, Ho WH, Maruoka M, IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1 [J].J Biol Chem.2001 Jan 12;276(2):1660-4.
[36]Allison J, Thomas H,Beck D, Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction [J].Int Immunol.2000 Jan;12(1):9-17.
[37]Wright JF, Guo Y,Quazi A,Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells [J]. See the search details. J Biol Chem.2007 May 4;282(18):13447-55. Epub 2007 Mar 13.
[38]Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses [J].Cell Res.2007 May;17(5):435-40.
[39]Yao Z, Painter SL, Fanslow WC, Human IL-17:a novel cytokine derived from T cells [J]. J Immunol.1995 Dec 15;155(12):5483-6.
[40]Fossiez F,Djossou O,Chomarat P,T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J]. J Exp Med.1996 Jun 1;183(6):2593-603.
[41]van den Berg A, Kuiper M, Snoek M, Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production to tumor necrosis factor-alpha in structural lung cells [J]. Am J Respir Cell Mol Biol.2005 Jul;33(1):97-104. Epub 2005 Apr 21.
[42]Bamba S,Andoh A,Yasui H,Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts:role of interleukin-17 [J]. J Gastroenterol.2003;38(6):548-54.
[43]Numasaki M,Fukushi J,Ono M,Interleukin-17 promotes angiogenesis and tumor growth [J]. Blood.2003 Apr 1;101(7):2620-7.Epub 2002 Oct 31.
[44]Thebault P, Lhermite N, Tilly G, The C-type lectin-like receptor CLEC-1, expressed by myeloid cells and endothelial cells, is up-regulated by immunoregulatory mediators and moderates T cell activation [J]. J Immunol.2009 Sep 1;183(5):3099-108. Epub 2009 Aug 10.
[45]Patel DN,King CA, Bailey SR, Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappaB and C/EBPbeta activation [J].J Biol Chem.2007 Sep 14;282(37):27229-38. Epub 2007 Jul 25.
[46]Cheng G, Wei L, Xiurong W, IL-17 stimulates migration of carotid artery vascular smooth muscle cells in an MMP-9 dependent manner via p38 MAPK and ERK1/2-dependent NF-kappaB and AP-1 activation [J]. Cell Mol Neurobiol.2009 Dec;29(8):1161-8.
[47]Yao Z, Spriggs MK, Derry JM, Molecular characterization of the human interleukin (IL)-17 receptor [J]. Cytokine.1997 Nov;9(11):794-800.
[48]Silva WA Jr, Covas DT, Panepucci RA, The profile of gene expression of human marrow mesenchymal stem cells [J]. Stem Cells.2003;21(6):661-9.
[49]Kuestner RE, Taft DW, Haran A, Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F [J]. J Immunol.2007 Oct 15;179(8):5462-73.
[50]Toy D, Kugler D, Wolfson M, Cutting edge:interleukin 17 signals through a heteromeric receptor complex [J]. J Immunol.2006 Jul 1;177(1):36-9.
[51]Novatchkova M, Leibbrandt A, Werzowa J, The STIR-domain superfamily in signal transduction, development and immunity [J].Trends Biochem Sci.2003 May;28(5):226-9.
[52]Miggin SM, Palsson-McDermott E, Dunne A, NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 [J]. Proc Natl Acad Sci U S A.2007 Feb 27;104(9):3372-7.Epub 2007 Feb 20.
[53]Maitra A,Shen F,Hanel W,Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression [J].Proc Natl Acad Sci U S A.2007 May 1;104(18):7506-11.Epub 2007 Apr 24.
[54]Qian Y,Liu C,Hartupee J,The adaptor Actl is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease [J].Nat Immunol.2007 Mar;8(3):247-56.Epub 2007 Feb 4.
[55]Sato S, Sanjo H, Takeda K, Essential function for the kinase TAK1 in innate and adaptive immune responses [J]. Nat Immunol.2005 Nov;6(11):1087-95. Epub 2005 Sep 25.
[56]Ruddy MJ, Wong GC,Liu XK,Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members [J]. J Biol Chem.2004 Jan 23;279(4):2559-67.Epub 2003 Nov 4.
[57]Awane M, Andres PG, Li DJ, NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells [J].J Immunol.1999 May 1;162(9):5337-44.
[58]Shen MM. Identification of differentially expressed genes in mouse development using differential display and in situ hybridization [J].Methods.2001 May;24(1):15-27.
[59]Costantino CM, Baecher-Allan CM, Hafler DA.Human regulatory T cells and autoimmunity [J]. Eur J Immunol.2008 Apr;38(4):921-4.
[60]Buckner JH, Ziegler SF. Functional analysis of FOXP3 [J]. Ann N Y Acad Sci.2008 Nov;1143:151-69.
[61]Horwitz DA,Zheng SG,Gray JD.Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other [J].Trends Immunol.2008 Sep;29(9):429-35. Epub 2008 Aug 3.
[62]Andre S, Tough DF, Lacroix-Desmazes S, Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity:immunopathogenesis and therapeutic implications [J]. Am J Pathol.2009 May;174(5):1575-87. Epub 2009 Apr 6.
[63]Valencia X, Lipsky PE. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases[J].Nat Clin Pract Rheumatol.2007 Nov;3(11):619-26.
[64]von Herrath MG, Harrison LC. Antigen-induced regulatory T cells in autoimmunity [J]. Nat Rev Immunol.2003 Mar;3(3):223-32.
[65]Yang XF. Factors regulating apoptosis and homeostasis of CD4+ CD25(high) FOXP3+ regulatory T cells are new therapeutic targets.Front Biosci.2008 Jan 1;13:1472-99.
[66]Zhou X, Bailey-Bucktrout SL, Jeker LT,Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo [J]. Nat Immunol.2009 Sep; 10(9):1000-7.Epub 2009 Jul 26.
[67]Kim JM,Rasmussen JP,Rudensky AY.Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice [J]. Nat Immunol.2007 Feb;8(2):191-7.Epub 2006 Nov 30.
[68]O'Connor RA, Malpass KH, Anderton SM. The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cells [J]. J Immunol.2007 Jul 15;179(2):958-66.
[69]Fletcher JM, Lonergan R, Costelloe L, CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis [J]. J Immunol.2009 Dec 1;183(11):7602-10.Epub 2009 Nov 16.
[70]Yang L, Anderson DE, Baecher-Allan C, IL-21 and TGF-beta are required for differentiation of human T(H)17 cells [J]. Nature.2008 Jul 17;454(7202):350-2. Epub 2008 May 11.
[71]Veldhoen M, Hocking RJ, Atkins CJ, TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells [J].Immunity.2006 Feb;24(2):179-89.
[72]Zhou L, Lopes JE, Chong MM,TGF-beta-induced Foxp3 inhibits T(H) 17 cell differentiation by antagonizing RORgammat function [J]. Nature.2008 May 8;453(7192):236-40. Epub 2008 Mar 26.
[73]Laurence A, Tato CM, Davidson TS, Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[74]Du J,Huang C,Zhou B,Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3 [J].J Immunol.2008 Apr 1;180(7):4785-92.
[75]Burchill MA, Yang J, Vogtenhuber C, IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells [J]. J Immunol.2007 Jan 1;178(1):280-90.
[76]Laurence A, Tato CM, Davidson TS, Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[77]Adamson AS, Collins K, Laurence A, The Current STATus of lymphocyte signaling:new roles for old players [J]. Curr Opin Immunol.2009 Apr;21(2):161-6. Epub 2009 Apr 9.
[78]Chen Z, Laurence A, Kanno Y,Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells [J]. Proc Natl Acad Sci U S A.2006 May 23;103(21):8137-42. Epub 2006 May 12.
[79]Quintana FJ,Basso AS,Iglesias AH, Control of T(reg) and T(H) 17 cell differentiation by the aryl hydrocarbon receptor [J]. Nature.2008 May 1;453(7191):65-71. Epub 2008 Mar 23.
[80]Happel KI, Dubin PJ, Zheng M, Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae [J]. J Exp Med.2005 Sep 19;202(6):761-9. Epub 2005 Sep 12.
[81]Wu Q,Martin RJ, Rino JG,IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection [J]. Microbes Infect.2007 Jan;9(1):78-86. Epub 2006 Dec 15.
[82]Tesmer LA, Lundy SK,Sarkar S,et al. Th17 cells in human disease [J]. Immunol Rev.2008 Jun;223:87-113.
[83]Oppenheim JJ, Biragyn A, Kwak LW, Roles of antimicrobial peptides such as defensins in innate and adaptive immunity [J].Ann Rheum Dis.2003 Nov;62 Suppl 2:ⅱ17-21.
[84]Chen Y, Thai P, Zhao YH, Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop [J]. J Biol Chem.2003 May 9;278(19):17036-43. Epub 2003 Mar 6.
[85]Luzza F, Parrello T, Monteleone G et al.Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa [J]. J Immunol 2000;165:5332-7.
[86]Ivanov S, Bozinovski S, Bossios A et al.Functional relevance of the IL-23-IL-17 axis in lungs in vivo [J]. Am J Respir Cell Mol Biol 2007;36:442-51.
[87]Liu J, Feng Y,Yang K,Early production of IL-17 protects against acute pulmonary Pseudomonas aeruginosa infection in mice [J]. FEMS Immunol Med Microbiol.2011 Mar;61(2):179-88.
[88]Honda T, Aoki Y, Takahashi N, Elevated expression of IL-17 and IL-12 genes in chronic inflammatory periodontal disease [J].Clin Chim Acta.2008 Sep;395(1-2):137-41. Epub 2008 Jun 8.
[89]Rapaka RR, Ricks DM, Alcorn JF,Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina [J]. J Exp Med.2010 Dec 20;207(13):2907-19. Epub 2010 Dec 13.
[90]Kudva A, Scheller EV, Robinson KM, Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice [J].J Immunol.2011 Feb 1;186(3):1666-74. Epub 2010 Dec 22.
[91]Mitchell GF. A note on concomitant immunity in host-parasite relationships:a successfully transplanted concept from tumor immunology [J]. Adv Cancer Res.1990;54:319-32.
[2]林洪远,盛志勇.我们需要一个更清晰的脓毒症概念和标准——介绍和评析2001年华盛顿国际脓毒症定义会议[J].中华外科杂志,2004,42(14)：836-838.
[3]Singh S, Evans TW. Organ dysfunction during sepsis [J]. Intensive Care Med, 2006,32(3):349-360.
[4]盛志勇,姚咏明.脓毒症研究的现状与展望[J].解放军医学杂志,1999,24(2)：79-82.
[5]Angus DC, Linde-Zwirble WT, Lidicker J, et al.Epidemiology of severe sepsis in the United States:analysis of incidence, outcome, and associated costs of care [J]. Crit Care Med.2001 Jul;29(7):1303-10.
[6]Brun-Buisson C, Roudot-Thoraval F, Girou E, et al.The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis [J]. Intensive Care Med.2003 Sep;29(9):1464-71.Epub 2003 Jul 10.
[7]姚咏明,柴家科,林洪远.现代脓毒症理论与实践[S].第1版.北京：科学出版社,2005,1-7.
[8]王正国.脓毒症研究概况[J].中华创伤杂志,2003,19(1)：5-8.
[9]李春盛.关于脓毒症的几个问题[J].中国危重病急救医学.2002,14(6)：323-328.
[10]Nagler-Anderson C, Bhan AK, Podolsky DK, el al. Control freaks:immune regulatory cells [J]. Nat Immunol.2004 Feb;5(2):119-22.
[11]Annunziato F, Cosmi L, Santarlasci V, Phenotypic and functional features of human Th17 cells [J]. J Exp Med.2007 Aug 6;204(8):1849-61. Epub 2007 Jul 16.
[12]Fazilleau N, Mark L, McHeyzer-Williams LJ, Follicular helper T cells:lineage and location [J]. Immunity.2009 Mar 20;30(3):324-35.
[13]Liang SC, Tan XY,Luxenberg DP,Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides[J]. J Exp Med.2006 Oct 2;203(10):2271-9. Epub 2006 Sep 18.
[14]Harris TJ, Grosso JF,Yen HR,Cutting edge:An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity [J].J Immunol.2007 Oct1;179(7):4313-7.
[15]Komiyama Y, Nakae S,Matsuki T, et al.IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].J Immunol.2006 Jul 1;177(1):566-73.
[16]Rao DA, Eid RE,Qin L, et al.Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection [J]. J Exp Med.2008 Dec 22;205(13):3145-58. Epub 2008 Dec 15.
[17]Paradowska A,Masliniski W,Grzybowska-Kowalczyk A,et al.The function of interleukin 17 in the pathogenesis of rheumatoid arthritis [J].Arch Immunol Ther Exp (Warsz).2007 Sep-Oct;55(5):329-34.
[18]Emamaullee JA, Davis J, Merani S, et al.Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice [J]. Diabetes.2009 Jun;58(6):1302-11. Epub 2009 Mar 16.
[19]Seene T,Kaasik P,Pehme A,et al.The effect of glucocorticoids on the myosin heavy chain isoforms turnover in skeletal muscle [J]. J Steroid Biochem Mol Biol.2003 Aug;86(2):201-6.
[20]Wang L, Luo GJ, Wang JJ, et al.Dexamethasone stimulates proteasome- and Calcium-dependent proteolysis in cultured L6 myocytes [J]. Shock.1998 Oct;10(4): 298-306.
[21]Bledsoe RK,Montana VG, Stanley TB. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition [J]. Cell,2002,110(1):93-105.
[22]Vegiopoulos A,Herzig S.Glucocorticoids, metabolism and metabolic diseases.Mol Cell Endocrinol[J].2007 Sep 15;275(1-2):43-61.Epub 2007 Jun 2.
[23]De Bosscher K, Beck IM, Haegeman G.Classic glucocorticoids versus non-steroidal glucocorticoid receptor modulators:survival of the fittest regulator of the immune system?Brain Behav Immun[J].2010 Oct;24(7):1035-42. Epub 2010 Jun 25.
[24]Heuer JG, Zhang T, Zhao J, Adoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis[J].J Immunol.2005 Jun 1;174(11):7141-6.
[25]唐朝晖,余彦,白祥军等,严重多发伤患者外周血CD4+CD25mgh调节性T细胞的变化及意义[J].中华创伤杂志,2008,24(2)：92-95.
[26]Mangan PR,Harrington LE,O'Quinn DB,Transforming growth factor-beta induces development of the T(H)17 lineage[J]. Nature.2006 May 11;441(7090):231-4. Epub 2006 Apr 30.
[27]Volpe E, Servant N, Zollinger R, A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating humanT(H)-17 responses[J]. Nat Immunol.2008 Jun;9(6):650-7. Epub 2008 May 4.
[28]Korn T, Oukka M, Kuchroo V, Th17 cells:effector T cells with inflammatory properties [J]. Semin Immunol.2007 Dec;19(6):362-71.Epub 2007 Nov 26.
[29]Komiyama Y, Nakae S, Matsuki T, IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis[J]. J Immunol.2006 Jul 1;177(1):566-73.
[30]Happel KI,Dubin PJ,Zheng M, Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae[J]. J Exp Med.2005 Sep 19;202(6):761-9. Epub 2005 Sep 12.
[31]Sergio L. Zanotti-Cavazzoni, Roy D. Animal Models of Sepsis[J]. Goldfarb, Crit Care Clin 25 (2009) 703-719
[32]Yao Z, Painter SL, Fanslow WC, Human IL-17:a novel cytokine derived from T cells. J Immunol[J].1995 Dec 15;155(12):5483-6.
[33]Fossiez F, Djossou O, Chomarat P, T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J]. J Exp Med.1996 Jun 1;183(6):2593-603.
[34]姚咏明.免疫功能紊乱在脓毒症发病中的作用及意义[J].中国危重病急救医学,2007,19(3)：138-141.
[35]Zhou L, Lopes JE, Chong MM, et al.TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function [J]. Nature.2008 May 8;453(7192):236-40. Epub 2008 Mar 26.
[36]Veldhoen M, Hocking RJ, Atkins CJ, et al. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells [J]. Immunity.2006 Feb;24(2):179-89.
[37]Laurence A, Tato CM, Davidson TS, et al. Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[38]Meakins JL, Pietsch JB, Bubenick O, et al. Delayed hypersensitivity:indicator of acquired failure of host defenses in sepsis and trauma [J]. Ann Surg.1977 sep; 186(3):241-50.
[39]Moore FA, Sauaia A,Moore EE, et al.Postinjury multiple organ failure:a bimodal phenomenon [J]. J Trauma 1996;40:501-510;dicussion,510-502
[40]Mannick JA, Rodrick ML, Lederer JA.The immunologic response to injury [J].J Am Coll Surg.2001 Sep;193(3):237-44.
[1]Korn T, Bettelli E, Oukka M, IL-17 and Th17 Cells [J]. Annu Rev Immunol.2009;27:485-517.
[2]Hue S,Ahern P,Buonocore S, et al.Interleukin-23 drives innate and T cell-mediated intestinal inflammation [J].J Exp Med.2006 Oct 30;203(11):2473-83.
[3]Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease [J]. Gut.2003 Jan;52(1):65-70.
[4]Csiszar A, Ungvari Z, Koller A,et al.Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries [J].FASEB J.2003 Jun;17(9): 1183-5. Epub 2003 Apr 22.
[5]Komiyama Y, Nakae S, Matsuki T, IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis [J].J Immunol.2006 Jul 1;177(1):566-73.
[6]Paradowska A, Masliniski W, Grzybowska-Kowalczyk A, The function of interleukin 17 in the pathogenesis of rheumatoid arthritis [J]. Arch Immunol Ther Exp (Warsz).2007 Sep-Oct;55(5):329-34.
[7]Jones CE, Chan K. Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells [J]. Am J Respir Cell Mol Biol.2002 Jun;26(6):748-53.
[8]Zhang Z, Zheng M, Bindas J, Critical role of IL-17 receptor signaling in acute TNBS-induced colitis [J]. Inflamm Bowel Dis.2006 May;12(5):382-8.
[9]Rao DA, Eid RE,Qin L, Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection [J]. J Exp Med.2008 Dec 22;205(13):3145-58. Epub 2008 Dec 15.
[10]Emamaullee JA, Davis J, Merani S, Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice [J]. Diabetes.2009 Jun;58(6):1302-11. Epub 2009 Mar 16.
[11]Mosmann TR, Coffman RL. TH1 and TH2 cells:different patterns of lymphokine secretion lead to different functional properties [J]. Annu Rev Immunol.1989;7:145-73.
[12]Annunziato F,Cosmi L,Santarlasci V,Phenotypic and functional features of human Th17 cells [J].J Exp Med.2007 Aug 6;204(8):1849-61. Epub 2007 Jul 16.
[13]Fazilleau N, Mark L, McHeyzer-Williams LJ, Follicular helper T cells:lineage and location [J]. Immunity.2009 Mar 20;30(3):324-35.
[14]Harrington LE, Hatton RD, Mangan PR, Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J]. Nat Immunol.2005 Nov;6(11):1123-32. Epub 2005 Oct 2.
[15]Liang SC, Tan XY, Luxenberg DP, Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides [J]. J Exp Med.2006 Oct 2;203(10):2271-9. Epub 2006 Sep 18.
[16]Cua DJ, Sherlock J, Chen Y, Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain [J]. Nature.2003 Feb 13;421(6924):744-8.
[17]Li MO, Wan YY,Flavell RA. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Thl-and Th17-cell differentiation [J].Immunity.2007 May;26(5):579-91. Epub 2007 May 3.
[18]Mangan PR, Harrington LE, O'Quinn DB,Transforming growth factor-beta induces development of the T(H) 17 lineage [J]. Nature.2006 May 11;441(7090):231-4. Epub 2006 Apr 30.
[19]Volpe E,Servant N,Zollinger R,A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses [J]. Nat Immunol.2008 Jun;9(6):650-7. Epub 2008 May 4.
[20]Langrish CL, Chen Y, Blumenschein WM, IL-23 drives a pathogenic T cell population that induces autoimmune inflammation [J]. J Exp Med.2005 Jan 17;201(2):233-40.
[21]Korn T, Oukka M, Kuchroo V,Th17 cells:effector T cells with inflammatory properties [J]. Semin Immunol.2007 Dec;19(6):362-71.Epub 2007 Nov 26.
[22]Bettelli E, Carrier Y, Gao W,Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature.2006 May 11;441(7090):235-8.Epub 2006 Apr 30.
[23]Wilson NJ, Boniface K, Chan JR,Development, cytokine profile and function of human interleukin 17-producing helper T cells [J]. Nat Immunol.2007 Sep;8(9):950-7. Epub 2007 Aug 5.
[24]Schraml BU, Hildner K,Ise W,The AP-1 transcription factor Batf controls T(H)17 differentiation [J]. Nature.2009 Jul 16;460(7253):405-9. Epub 2009 Jul 5.
[25]Harris TJ, Grosso JF, Yen HR, Cutting edge:An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity [J]. J Immunol.2007 Oct 1;179(7):4313-7.
[26]McGeachy MJ, Chen Y, Tato CM, The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo [J]. Nat Immunol.2009 Mar; 10(3):314-24. Epub 2009 Feb 1.
[27]Nurieva R, Yang XO,Martinez G, Essential autocrine regulation by IL-21 in the generation of inflammatory T cells [J]. Nature.2007 Jul 26;448(7152):480-3. Epub 2007 Jun 20.
[28]Korn T,Bettelli E,Gao W, IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells [J]. Nature.2007 Jul 26;448(7152):484-7. Epub 2007 Jun 20.
[29]Zhou L,Ivanov II,Spolski R,IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways [J]. Nat Immunol.2007 Sep;8(9):967-74. Epub 2007 Jun 20.
[30]Szabo SJ, Sullivan BM, Peng SL, Molecular mechanisms regulating Thl immune responses [J]. Annu Rev Immunol.2003;21:713-58. Epub 2001 Dec 19.
[31]Glimcher LH, Murphy KM. Lineage commitment in the immune system:the T helper lymphocyte grows up [J]. Genes Dev.2000 Jul 15; 14(14):1693-711.
[32]Park H, Li Z,Yang XO,Chang SH, A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 [J]. Nat Immunol.2005 Nov;6(11):1133-41.Epub 2005 Oct 2.
[33]Sundrud MS, Koralov SB,Feuerer M,Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response [J]. Science.2009 Jun 5;324(5932):1334-8.
[34]Rouvier E,Luciani MF,Mattei MG,CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene [J]. J Immunol.1993 Jun 15;150(12):5445-56.
[35]Lee J, Ho WH, Maruoka M, IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1 [J].J Biol Chem.2001 Jan 12;276(2):1660-4.
[36]Allison J, Thomas H,Beck D, Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction [J].Int Immunol.2000 Jan;12(1):9-17.
[37]Wright JF, Guo Y,Quazi A,Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells [J]. See the search details. J Biol Chem.2007 May 4;282(18):13447-55. Epub 2007 Mar 13.
[38]Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses [J].Cell Res.2007 May;17(5):435-40.
[39]Yao Z, Painter SL, Fanslow WC, Human IL-17:a novel cytokine derived from T cells [J]. J Immunol.1995 Dec 15;155(12):5483-6.
[40]Fossiez F,Djossou O,Chomarat P,T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J]. J Exp Med.1996 Jun 1;183(6):2593-603.
[41]van den Berg A, Kuiper M, Snoek M, Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production to tumor necrosis factor-alpha in structural lung cells [J]. Am J Respir Cell Mol Biol.2005 Jul;33(1):97-104. Epub 2005 Apr 21.
[42]Bamba S,Andoh A,Yasui H,Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts:role of interleukin-17 [J]. J Gastroenterol.2003;38(6):548-54.
[43]Numasaki M,Fukushi J,Ono M,Interleukin-17 promotes angiogenesis and tumor growth [J]. Blood.2003 Apr 1;101(7):2620-7.Epub 2002 Oct 31.
[44]Thebault P, Lhermite N, Tilly G, The C-type lectin-like receptor CLEC-1, expressed by myeloid cells and endothelial cells, is up-regulated by immunoregulatory mediators and moderates T cell activation [J]. J Immunol.2009 Sep 1;183(5):3099-108. Epub 2009 Aug 10.
[45]Patel DN,King CA, Bailey SR, Interleukin-17 stimulates C-reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2-dependent NF-kappaB and C/EBPbeta activation [J].J Biol Chem.2007 Sep 14;282(37):27229-38. Epub 2007 Jul 25.
[46]Cheng G, Wei L, Xiurong W, IL-17 stimulates migration of carotid artery vascular smooth muscle cells in an MMP-9 dependent manner via p38 MAPK and ERK1/2-dependent NF-kappaB and AP-1 activation [J]. Cell Mol Neurobiol.2009 Dec;29(8):1161-8.
[47]Yao Z, Spriggs MK, Derry JM, Molecular characterization of the human interleukin (IL)-17 receptor [J]. Cytokine.1997 Nov;9(11):794-800.
[48]Silva WA Jr, Covas DT, Panepucci RA, The profile of gene expression of human marrow mesenchymal stem cells [J]. Stem Cells.2003;21(6):661-9.
[49]Kuestner RE, Taft DW, Haran A, Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F [J]. J Immunol.2007 Oct 15;179(8):5462-73.
[50]Toy D, Kugler D, Wolfson M, Cutting edge:interleukin 17 signals through a heteromeric receptor complex [J]. J Immunol.2006 Jul 1;177(1):36-9.
[51]Novatchkova M, Leibbrandt A, Werzowa J, The STIR-domain superfamily in signal transduction, development and immunity [J].Trends Biochem Sci.2003 May;28(5):226-9.
[52]Miggin SM, Palsson-McDermott E, Dunne A, NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1 [J]. Proc Natl Acad Sci U S A.2007 Feb 27;104(9):3372-7.Epub 2007 Feb 20.
[53]Maitra A,Shen F,Hanel W,Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression [J].Proc Natl Acad Sci U S A.2007 May 1;104(18):7506-11.Epub 2007 Apr 24.
[54]Qian Y,Liu C,Hartupee J,The adaptor Actl is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease [J].Nat Immunol.2007 Mar;8(3):247-56.Epub 2007 Feb 4.
[55]Sato S, Sanjo H, Takeda K, Essential function for the kinase TAK1 in innate and adaptive immune responses [J]. Nat Immunol.2005 Nov;6(11):1087-95. Epub 2005 Sep 25.
[56]Ruddy MJ, Wong GC,Liu XK,Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT/enhancer-binding protein family members [J]. J Biol Chem.2004 Jan 23;279(4):2559-67.Epub 2003 Nov 4.
[57]Awane M, Andres PG, Li DJ, NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells [J].J Immunol.1999 May 1;162(9):5337-44.
[58]Shen MM. Identification of differentially expressed genes in mouse development using differential display and in situ hybridization [J].Methods.2001 May;24(1):15-27.
[59]Costantino CM, Baecher-Allan CM, Hafler DA.Human regulatory T cells and autoimmunity [J]. Eur J Immunol.2008 Apr;38(4):921-4.
[60]Buckner JH, Ziegler SF. Functional analysis of FOXP3 [J]. Ann N Y Acad Sci.2008 Nov;1143:151-69.
[61]Horwitz DA,Zheng SG,Gray JD.Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other [J].Trends Immunol.2008 Sep;29(9):429-35. Epub 2008 Aug 3.
[62]Andre S, Tough DF, Lacroix-Desmazes S, Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity:immunopathogenesis and therapeutic implications [J]. Am J Pathol.2009 May;174(5):1575-87. Epub 2009 Apr 6.
[63]Valencia X, Lipsky PE. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases[J].Nat Clin Pract Rheumatol.2007 Nov;3(11):619-26.
[64]von Herrath MG, Harrison LC. Antigen-induced regulatory T cells in autoimmunity [J]. Nat Rev Immunol.2003 Mar;3(3):223-32.
[65]Yang XF. Factors regulating apoptosis and homeostasis of CD4+ CD25(high) FOXP3+ regulatory T cells are new therapeutic targets.Front Biosci.2008 Jan 1;13:1472-99.
[66]Zhou X, Bailey-Bucktrout SL, Jeker LT,Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo [J]. Nat Immunol.2009 Sep; 10(9):1000-7.Epub 2009 Jul 26.
[67]Kim JM,Rasmussen JP,Rudensky AY.Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice [J]. Nat Immunol.2007 Feb;8(2):191-7.Epub 2006 Nov 30.
[68]O'Connor RA, Malpass KH, Anderton SM. The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cells [J]. J Immunol.2007 Jul 15;179(2):958-66.
[69]Fletcher JM, Lonergan R, Costelloe L, CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis [J]. J Immunol.2009 Dec 1;183(11):7602-10.Epub 2009 Nov 16.
[70]Yang L, Anderson DE, Baecher-Allan C, IL-21 and TGF-beta are required for differentiation of human T(H)17 cells [J]. Nature.2008 Jul 17;454(7202):350-2. Epub 2008 May 11.
[71]Veldhoen M, Hocking RJ, Atkins CJ, TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells [J].Immunity.2006 Feb;24(2):179-89.
[72]Zhou L, Lopes JE, Chong MM,TGF-beta-induced Foxp3 inhibits T(H) 17 cell differentiation by antagonizing RORgammat function [J]. Nature.2008 May 8;453(7192):236-40. Epub 2008 Mar 26.
[73]Laurence A, Tato CM, Davidson TS, Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[74]Du J,Huang C,Zhou B,Isoform-specific inhibition of ROR alpha-mediated transcriptional activation by human FOXP3 [J].J Immunol.2008 Apr 1;180(7):4785-92.
[75]Burchill MA, Yang J, Vogtenhuber C, IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells [J]. J Immunol.2007 Jan 1;178(1):280-90.
[76]Laurence A, Tato CM, Davidson TS, Interleukin-2 signaling via STAT5 constrains Thelper 17 cell generation [J]. Immunity.2007 Mar;26(3):371-81.
[77]Adamson AS, Collins K, Laurence A, The Current STATus of lymphocyte signaling:new roles for old players [J]. Curr Opin Immunol.2009 Apr;21(2):161-6. Epub 2009 Apr 9.
[78]Chen Z, Laurence A, Kanno Y,Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells [J]. Proc Natl Acad Sci U S A.2006 May 23;103(21):8137-42. Epub 2006 May 12.
[79]Quintana FJ,Basso AS,Iglesias AH, Control of T(reg) and T(H) 17 cell differentiation by the aryl hydrocarbon receptor [J]. Nature.2008 May 1;453(7191):65-71. Epub 2008 Mar 23.
[80]Happel KI, Dubin PJ, Zheng M, Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae [J]. J Exp Med.2005 Sep 19;202(6):761-9. Epub 2005 Sep 12.
[81]Wu Q,Martin RJ, Rino JG,IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection [J]. Microbes Infect.2007 Jan;9(1):78-86. Epub 2006 Dec 15.
[82]Tesmer LA, Lundy SK,Sarkar S,et al. Th17 cells in human disease [J]. Immunol Rev.2008 Jun;223:87-113.
[83]Oppenheim JJ, Biragyn A, Kwak LW, Roles of antimicrobial peptides such as defensins in innate and adaptive immunity [J].Ann Rheum Dis.2003 Nov;62 Suppl 2:ⅱ17-21.
[84]Chen Y, Thai P, Zhao YH, Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop [J]. J Biol Chem.2003 May 9;278(19):17036-43. Epub 2003 Mar 6.
[85]Luzza F, Parrello T, Monteleone G et al.Up-regulation of IL-17 is associated with bioactive IL-8 expression in Helicobacter pylori-infected human gastric mucosa [J]. J Immunol 2000;165:5332-7.
[86]Ivanov S, Bozinovski S, Bossios A et al.Functional relevance of the IL-23-IL-17 axis in lungs in vivo [J]. Am J Respir Cell Mol Biol 2007;36:442-51.
[87]Liu J, Feng Y,Yang K,Early production of IL-17 protects against acute pulmonary Pseudomonas aeruginosa infection in mice [J]. FEMS Immunol Med Microbiol.2011 Mar;61(2):179-88.
[88]Honda T, Aoki Y, Takahashi N, Elevated expression of IL-17 and IL-12 genes in chronic inflammatory periodontal disease [J].Clin Chim Acta.2008 Sep;395(1-2):137-41. Epub 2008 Jun 8.
[89]Rapaka RR, Ricks DM, Alcorn JF,Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina [J]. J Exp Med.2010 Dec 20;207(13):2907-19. Epub 2010 Dec 13.
[90]Kudva A, Scheller EV, Robinson KM, Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice [J].J Immunol.2011 Feb 1;186(3):1666-74. Epub 2010 Dec 22.
[91]Mitchell GF. A note on concomitant immunity in host-parasite relationships:a successfully transplanted concept from tumor immunology [J]. Adv Cancer Res.1990;54:319-32.