摘要
目的研究T细胞亚型相关的五种细胞因子IFN-γ、IL-4、IL-17、IL-10、TGF-β在鼻息肉中的表达情况,探讨各种细胞因子在过敏与非过敏性鼻息肉形成过程中所起作用。
方法研究对象包括非过敏组10例,过敏组15例,正常对照组10例。采用免疫组织化学荧光检测法研究五种细胞因子在过敏与非过敏性鼻息肉形态学表达上的差异,Western Blot方法定量测定细胞因子IFN-γ、IL-4、IL-17、IL-10、TGF-β的蛋白表达水平。
结果免疫荧光检测结果显示IFN-γ、IL-4、IL-10、TGF-β在非过敏组与过敏组鼻息肉粘膜下均有较明显的表达,而IL-17在过敏组表达较非过敏组明显。Western Blot结果显示过敏组、非过敏组IFN-γ、IL-4、TGF-β蛋白表达水平均较正常组升高(P<0.05),但两组间蛋白表达量并无明显统计学意义(P>0.05)。而正常组、过敏组与非过敏组三组间IL-17和IL-10蛋白表达水平均无明显统计学意义(P>0.05)。
结论过敏性、非过敏性鼻息肉中细胞因子IFN-γ、IL-4、TGF-β表达均增多,可能在鼻息肉的炎症反应过程中起着重要的作用。IL-17和IL-10蛋白变化不明显。T细胞亚型相关细胞因子在过敏与非过敏性鼻息肉中的蛋白表达无明显差异性。
目的研究T细胞亚型四种特异性转录因子T-bet、GATA-3、RORγt、Foxp3基因的定量表达,探讨四种基因在过敏与非过敏性鼻息肉的形成过程中所起的作用。
方法研究对象包括非过敏组10例,过敏组20例,正常对照组10例。采用定量PCR分析四种基因的转录情况,比较其在过敏与非过敏性鼻息肉中表达的差异性。
结果非过敏组T-bet基因表达水平较正常组、过敏组均有升高,差别具有统计学意义(P<0.05),但过敏组与正常组相比无明显统计学意义(P>0.05)。非过敏组GATA-3基因表达水平较正常组升高,差别具有统计学意义(P<0.05),而过敏组与正常组、非过敏组之间均无明显统计学意义(P>0.05)。正常组、非过敏组与过敏组三组之间RORγt、Foxp3基因表达水平无明显统计学意义(P>0.05),但非过敏组RORγt基因表达水平有明显升高趋势,过敏组与非过敏组Foxp3基因表达水平较正常组有明显降低趋势。
结论非过敏性鼻息肉T-bet、GATA-3基因表达水平升高,过敏与非过敏性鼻息肉Foxp3基因表达水平均有降低趋势。T细胞亚型特异性因子除T-bet基因外GATA-3、RORγt、Foxp3在过敏与非过敏性鼻息肉中的表达均无明显差异性。Th1、Th2、Th17细胞可能在非过敏性鼻息肉的发病过程中起着更为重要的作用,Treg细胞可能对过敏与非过敏性鼻息肉均有抑制作用。
Objectives:To quantificate the expression of T-cell related cytokines in nasal polyps and explore their roles in the development of allergic and non-allergic nasal polyps.
Methods:Ten allergic and fifteen non-allergic patients with nasal polyps were studied. The T-cell subtype cytokines (IL-4, interferon [IFN]γ, IL-10, IL-17, and transforming growth factor [TGF]β) were analyzed by immunofluorescence. The levels of cytokine proteins were measured by Western Blot.
Results:IFN-γ, IL-4, IL-10 and TGF-βwere expressed apparently in submucosa of all patients, but IL-17 was not easily observed in non-allergic ones by immunofluorescence. Increased levels of IFN-γ, IL-4 and TGF-βwere found in both allergic and non-allergic nasal polyps compared with control tissues (P< 0.05) However, there was no significances between them (P>0.05). Furthermore, the levels of IL-17 and IL-10 have no differences among contol tissues, allergic and non-allergic nasal polyps (P>0.05)
Conclusions:Increased levels of IFN-γ, IL-4 and TGF-βwere found in both allergic and non-allergic nasal polyps, which suggested IFN-γ, IL-4 and TGF-βmay play important roles in the inflammation of nasal polyps. There was no differences of T-cell cytokines between allergic and non-allergic nasal polyps.
Objectives:To quantificate the gene expression of T-cell Subtype characterized transcription factors in nasal polyps and explore their roles in the development of allergic and non-allergic nasal polyps.
Methods:Ten allergic and twenty non-allergic patients with nasal polyps were studied. Expression of T-bet, GATA-3, Foxp3, and RORγt mRNA was detected by real-time polymerase chain reaction.
Results:Expression of T-bet and GATA-3 mRNA was upregulated in non-allergic nasal polyps (P< 0.05). There was no significant differences on levels of T-bet and GATA-3 mRNA between allergic nasal polyps and control tissues (P>0.05). The levels of RORγt、Foxp3 mRNA have no differences among contol tissues, allergic and non-allergic nasal polyps (P>0.05). But markedly upregulated tendency of ROR Y t mRNA was showed in non-allergic ones and downregulated tendency of Foxp3 mRNA was manifested in all patients. Only the level of T-bet mRNA of non-allergic polyps was higher than allergic nasal ones (P< 0.05)
Conclusions:The findings demonstrated that Th1, Th2 and Th17 cell may play a more important role in non-allergic nasal polyps. Treg cell was likely to inhibit the development of both allergic and non-allergic nasal polyps.
引文
[1]Anand VK. Epidemiology and economic impact of rhinosinusitis. Ann Otol Rhinol Laryngol Suppl.2004,193:3-5.
[2]Ramanathan M Jr, Spannhake EW, Lane AP. Chronic rhinosinusitis with nasal polyps is associated with decreased expression of mucosal interleukin 22 receptor. Laryngoscope.2007,117(10):1839-43.
[3]Pant H, Ferguson BJ, Macardle PJ. The role of allergy in rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg.2009,17(3):232-8.
[4]Otto BA, Wenzel SE. The role of cytokines in chronic rhinosinusitis with nasal polyps. Curr Opin Otolaryngol Head Neck Surg.2008,16(3):270-4.
[5]Kim JW, Hong SL, Kim YK, et al. Histological and immunological features of non-eosinophilic nasal polyps. Otolaryngol Head Neck Surg. 2007,137(6):925-30.
[6]Hao J, Pang YT, Wang DY. Diffuse mucosal inflammation in nasal polyps and adjacent middle turbinate. Otolaryngol Head Neck Surg. 2006,134(2):267-75.
[7]Zhang N, Holtappels G, Claeys C, et al. Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China. Am J Rhinol.2006,20(4):445-50.
[8]Mesquita Jr D, Cruvinel WM, Camara NO, et al. Autoimmune diseases in the TH17 era. Braz J Med Biol Res.2009,42(6):476-86.
[9]Alcorn JF, Crowe CR, Kolls JK. TH17 cells in asthma and COPD. Annu Rev Physiol.2010,72:495-516.
[10]Siwiec J, Zaborowski T, Jankowska O, et al. Evaluation of Thl/Th2 lymphocyte balance and lipopolysaccharide receptor expression in asthma patients. Pneumonol Alergol Pol.2009,77(2):123-30.
[11]Kearley J, Barker JE, Robinson DS, et al. Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med.2005,202(11):1539-47. Epub 2005 Nov 28.
[12]Kearley J, Robinson DS, Lloyd CM. CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling. J Allergy Clin Immunol.2008,122(3):617-24.e6. Epub 2008 Jul 30.
[13]Cheng W, Zheng C, Tian J, et al. T helper cell population and eosinophilia in nasal polyps. J Investig Allergol Clin Immunol.2007,17(5):297-301.
[14]Shi J, Fan Y, Xu R, et al. Characterizing T-cell phenotypes in nasal polyposis in Chinese patients. J Investig Allergol Clin Immunol.2009,19(4):276-82.
[15]Bachert C, Gevaert P, Holtappels G, et al. Nasal polyposis:from cytokines to growth. Am J Rhinol.2000,14(5):279-90.
[16]Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma:an overview of signals, mechanisms and functions. J Leukoc Biol.2004,75(2):163-89. Epub 2003 Oct 2.
[17]Nakajima H, Takatsu K. Role of cytokines in allergic airway inflammation. Int Arch Allergy Immunol.2007,142(4):265-73. Epub 2006 Nov 22.
[18]Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006,61(11):1280-9.
[19]Danielsen A, Tynning T, Brokstad KA, et al. Interleukin 5, IL6, IL12, IFN-gamma, RANTES and Fractalkine in human nasal polyps, turbinate mucosa and serum. Eur Arch Otorhinolaryngol.2006,263(3):282-9. Epub 2006 Feb 3.
[20]Bachert C, Gevaert P, Holtappels G, et al. Mediators in nasal polyposis. Curr Allergy Asthma Rep.2002,2(6):481-7.
[21]Nouri-Aria KT, Irani AM, Jacobson MR, et al. Basophil recruitment and IL-4 production during human allergen-induced late asthma. J Allergy Clin Immunol.2001,108(2):205-11.
[22]Yea SS, Yang YI, Park SK, et al. Interleukin-4 C-590T polymorphism is associated with protection against nasal polyps in a Korean population. Am J Rhinol.2006,20(5):550-3.
[23]Bradley DT, Kountakis SE. Role of interleukins and transforming growth factor-beta in chronic rhinosinusitis and nasal polyposis. Laryngoscope. 2005,115(4):684-6.
[24]Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum.2009,60(5):1472-83.
[25]Di Stefano A, Caramori G, Gnemmi I, et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol.2009,157(2):316-24.
[26]Klemens C, Rasp G, Jund F, et al. Mediators and cytokines in allergic and viral-triggered rhinitis. Allergy Asthma Proc.2007,28(4):434-41.
[27]Oboki K, Ohno T, Saito H, et al. Th17 and allergy. Allergol Int. 2008,57(2):121-34.
[28]Van Bruaene N, Perez-Novo CA, Basinski TM, et al. T-cell regulation in chronic paranasal sinus disease. J Allergy Clin Immunol. 2008,121(6):1435-41,1441.e1-3.
[29]Robinson DS. Regulatory T cells and asthma. Clin Exp Allergy. 2009,39(9):1314-23. Epub 2009 Jun 17.
[30]Oh JW, Seroogy CM, Meyer EH, et al. CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation. J Allergy Clin Immunol.2002,110(3):460-8.
[31]Till SJ, Francis JN, Nouri-Aria K, et al. Mechanisms of immunotherapy. J Allergy Clin Immunol.2004,113(6):1025-34; quiz 1035.
[32]Coste A, Lefaucheur JP, Wang QP, et al. Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps. Arch Otolaryngol Head Neck Surg.1998,124(12):1361-6.
[33]Little SC, Early SB, Woodard CR, et al. Dual action of TGF-betal on nasal-polyp derived fibroblasts. Laryngoscope.2008,118(2):320-4.
[34]Li MO, Wan YY, Sanjabi S, et al. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol.2006,24:99-146.
[35]Watelet JB, Claeys C, Perez-Novo C, et al. Transforming growth factor betal in nasal remodeling:differences between chronic rhinosinusitis and nasal polyposis. Am J Rhinol.2004,18(5):267-72.
[36]Elovic A, Wong DT, Weller PF, et al. Expression of transforming growth factors-alpha and beta 1 messenger RNA and product by eosinophils in nasal polyps. J Allergy Clin Immunol.1994,93(5):864-9.
[37]Larsen PL, Tos M, Kuijpers W, et al. The early stages of polyp formation. Laryngoscope.1992,102(6):670-7.
[38]Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Thl lineage commitment. Cell.2000,100(6):655-69.
[39]Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997,89(4):587-96.
[40]Ivanov Ⅱ, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell.2006,126(6):1121-33.
[41]Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003,4(4):330-6. Epub 2003 Mar 3.
[42]Nakamura Y, Christodoulopoulos P, Cameron L, et al. Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge. J Allergy Clin Immunol.2000,105(6 Pt 1):1146-52.
[43]Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol. 1999,103(2 Pt 1):215-22.
[44]Ferber IA, Lee HJ, Zonin F, et al. GATA-3 significantly downregulates IFN-gamma production from developing Thl cells in addition to inducing IL-4 and IL-5 levels. Clin Immunol.1999,91(2):134-44.
[45]Zhu J, Yamane H, Cote-Sierra J, et al. GATA-3 promotes Th2 responses through three different mechanisms:induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Thl cell-specific factors. Cell Res.2006,16(1):3-10.
[46]Taghon T, Yui MA, Rothenberg EV. Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nat Immunol. 2007,8(8):845-55. Epub 2007 Jul 1.
[47]Schmidt-Weber CB, Akdis M, Akdis CA. TH17 cells in the big picture of immunology. J Allergy Clin Immunol.2007,120(2):247-54.
[48]Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science.2003,299(5609):1057-61. Epub 2003 Jan 9.
[49]Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet.2001,27(1):20-1.
[50]Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked:forkhead box protein 3 mutations and lack of regulatory T cells. J Allergy Clin Immunol.2007,120(4):744-50; quiz 751-2.
[51]Xu G, Mou Z, Jiang H, et al. A possible role of CD4+CD25+ T cells as well as transcription factor Foxp3 in the dysregulation of allergic rhinitis. Laryngoscope.2007,117(5):876-80.
[52]Umetsu DT, DeKruyff RH. The regulation of allergy and asthma. Immunol Rev.2006,212:238-55.
[53]Li HB, Cai KM, Liu Z, et al. Foxp3+ T regulatory cells (Tregs) are increased in nasal polyps (NP) after treatment with intranasal steroid. Clin Immunol. 2008,129(3):394-400. Epub 2008 Sep 14.
[1]Mosmann TR, Coffman RL. TH1 and TH2 cells:different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol.1989,7:145-73.
[2]Mesquita Jr D, Cruvinel WM, Camara NO, et al. Autoimmune diseases in the TH17 era. Braz J Med Biol Res.2009,42(6):476-86.
[3]Alcorn JF, Crowe CR, Kolls JK. TH17 cells in asthma and COPD. Annu Rev Physiol.2010,72:495-516.
[4]Siwiec J, Zaborowski T, Jankowska 0, et al. [Evaluation of Thl/Th2 lymphocyte balance and lipopolysaccharide receptor expression in asthma patients]. Pneumonol Alergol Pol.2009,77(2):123-30.
[5]Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma:an overview of signals, mechanisms and functions. J Leukoc Biol.2004,75(2):163-89. Epub 2003 Oct 2.
[6]Nakajima H, Takatsu K. Role of cytokines in allergic airway inflammation. Int Arch Allergy Immunol.2007,142(4):265-73. Epub 2006 Nov 22.
[7]Van Zele T, Claeys S, Gevaert P, et al. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006,61 (11):1280-9.
[8]Randolph DA, Stephens R, Carruthers CJ, et al. Cooperation between Thl and Th2 cells in a murine model of eosinophilic airway inflammation. J Clin Invest.1999,104(8):1021-9.
[9]Danielsen A, Tynning T, Brokstad KA, et al. Interleukin 5, IL6, IL12, IFN-gamma, RANTES and Fractalkine in human nasal polyps, turbinate mucosa and serum. Eur Arch Otorhinolaryngol.2006,263(3):282-9. Epub 2006 Feb 3.
[10]Cheng W, Zheng C, Tian J, et al. T helper cell population and eosinophilia in nasal polyps. J Investig Allergol Clin Immunol.2007,17(5):297-301.
[11]Bachert C, Gevaert P, Holtappels G, et al. Mediators in nasal polyposis. Curr Allergy Asthma Rep.2002,2(6):481-7.
[12]Shi J, Fan Y, Xu R, et al. Characterizing T-cell phenotypes in nasal polyposis in Chinese patients. J Investig Allergol Clin Immunol.2009,19(4):276-82.
[13]Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Thl lineage commitment. Cell.2000,100(6):655-69.
[14]Van Bruaene N, Perez-Novo CA, Basinski TM, et al. T-cell regulation in chronic paranasal sinus disease. J Allergy Clin Immunol. 2008,121(6):1435-41,1441.e1-3.
[15]Di Sabatino A, Pickard KM, Rampton D, et al. Blockade of transforming growth factor beta upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa. Gut.2008,57(5):605-12. Epub 2008 Jan 4.
[16]Monteleone I, Monteleone G, Del Vecchio Blanco G, et al. Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa. Gut. 2004,53(8):1090-5.
[17]Neurath MF, Weigmann B, Finotto S, et al. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J Exp Med.2002,195(9):1129-43.
[18]Douwes J, Gibson P, Pekkanen J, et al. Non-eosinophilic asthma:importance and possible mechanisms. Thorax.2002,57(7):643-8.
[19]Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma:evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest.2001,119(5):1329-36.
[20]Louis R, Lau LC, Bron AO, et al. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000,161(1):9-16.
[21]Woodruff PG, Khashayar R, Lazarus SC, et al. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J Allergy Clin Immunol.2001,108(5):753-8.
[22]Tsokos M, Paulsen F. Expression of pulmonary lactoferrin in sudden-onset and slow-onset asthma with fatal outcome. Virchows Arch. 2002,441(5):494-9. Epub 2002 Jun 26.
[23]Lamblin C, Gosset P, Tillie-Leblond I, et al. Bronchial neutrophilia in patients with noninfectious status asthmaticus. Am J Respir Crit Care Med. 1998,157(2):394-402.
[24]Leung DY, Spahn JD, Szefler SJ. Steroid-unresponsive asthma. Semin Respir Crit Care Med.2002,23(4):387-98.
[25]Nouri-Aria KT, Irani AM, Jacobson MR, et al. Basophil recruitment and IL-4 production during human allergen-induced late asthma. J Allergy Clin Immunol.2001,108(2):205-11.
[26]Yea SS, Yang YI, Park SK, et al. Interleukin-4 C-590T polymorphism is associated with protection against nasal polyps in a Korean population. Am J Rhinol.2006,20(5):550-3.
[27]Bradley DT, Kountakis SE. Role of interleukins and transforming growth factor-beta in chronic rhinosinusitis and nasal polyposis. Laryngoscope. 2005,115(4):684-6.
[28]Nakamura Y, Christodoulopoulos P, Cameron L, et al. Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge. J Allergy Clin Immunol.2000,105(6 Pt 1):1146-52.
[29]Nakamura Y, Ghaffar O, Olivenstein R, et al. Gene expression of the GATA-3 transcription factor is increased in atopic asthma. J Allergy Clin Immunol. 1999,103(2 Pt 1):215-22.
[30]Ferber IA, Lee HJ, Zonin F, et al. GATA-3 significantly downregulates IFN-gamma production from developing Thl cells in addition to inducing IL-4 and IL-5 levels. Clin Immunol.1999,91(2):134-44.
[31]Zhu J, Yamane H, Cote-Sierra J, et al. GATA-3 promotes Th2 responses through three different mechanisms:induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Thl cell-specific factors. Cell Res.2006,16(1):3-10.
[32]Ochs HD, Oukka M, Torgerson TR. TH17 cells and regulatory T cells in primary immunodeficiency diseases. J Allergy Clin Immunol. 2009,123(5):977-83; quiz 984-5.
[33]Yao Z, Painter SL, Fanslow WC, et al. Human IL-17:a novel cytokine derived from T cells. J Immunol.1995,155(12):5483-6.
[34]Weaver CT, Harrington LE, Mangan PR, et al. Th17:an effector CD4 T cell lineage with regulatory T cell ties. Immunity.2006,24(6):677-88.
[35]Kawaguchi M, Adachi M, Oda N, et al. IL-17 cytokine family. J Allergy Clin Immunol.2004,114(6):1265-73; quiz 1274.
[36]Molet S, Hamid Q, Davoine F, et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol.2001,108(3):430-8.
[37]Laan M, Palmberg L, Larsson K, et al. Free, soluble interleukin-17 protein during severe inflammation in human airways. Eur Respir J. 2002,19(3):534-7.
[38]Sergejeva S, Ivanov S, Lotvall J, et al. Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. Am J Respir Cell Mol Biol.2005,33(3):248-53. Epub 2005 May 18.
[39]Ye P, Rodriguez FH, Kanaly S, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001,194(4):519-27.
[40]Wu Q, Martin RJ, Rino JG, et al. IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection. Microbes Infect. 2007,9(1):78-86. Epub 2006 Dec 15.
[41]Crowe CR, Chen K, Pociask DA, et al. Critical role of IL-17RA in immunopathology of influenza infection. J Immunol.2009,183(8):5301-10. Epub 2009 Sep 25.
[42]Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum.2009,60(5):1472-83.
[43]Di Stefano A, Caramori G, Gnemmi I, et al. T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol.2009,157(2):316-24.
[44]Klemens C, Rasp G, Jund F, et al. Mediators and cytokines in allergic and viral-triggered rhinitis. Allergy Asthma Proc.2007,28(4):434-41.
[45]Oboki K, Ohno T, Saito H, et al. Th17 and allergy. Allergol Int. 2008,57(2):121-34.
[46]Schmidt-Weber CB, Akdis M, Akdis CA. TH17 cells in the big picture of immunology. J Allergy Clin Immunol.2007,120(2):247-54.
[47]Kearley J, Barker JE, Robinson DS, et al. Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent. J Exp Med.2005,202(11):1539-47. Epub 2005 Nov 28.
[48]Kearley J, Robinson DS, Lloyd CM. CD4+CD25+ rgulatory T cells reverse established allergic airway inflammation and prevent airway remodeling. J Allergy Clin Immunol.2008,122(3):617-24.e6. Epub 2008 Jul 30.
[49]Coste A, Lefaucheur JP, Wang QP, et al. Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps. Arch Otolaryngol Head Neck Surg.1998,124(12):1361-6.
[50]Little SC, Early SB, Woodard CR, et al. Dual action of TGF-betal on nasal-polyp derived fibroblasts. Laryngoscope.2008,118(2):320-4.
[51]Li MO, Wan YY, Sanjabi S, et al. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol.2006,24:99-146.
[52]Watelet JB, Claeys C, Perez-Novo C, et al.Transforming growth factor betal in nasal remodeling:differences between chronic rhinosinusitis and nasal polyposis. Am J Rhinol.2004,18(5):267-72.
[53]Chu HW, Balzar S, Seedorf GJ, et al. Transforming growth factor-beta2 induces bronchial epithelial mucin expression in asthma. Am J Pathol. 2004,165(4):1097-106.
[54]Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med.2003,198(12):1875-86.
[55]Bachert C, Gevaert P, Holtappels G, et al. Nasal polyposis:from cytokines to growth. Am J Rhinol.2000,14(5):279-90.
[56]Coste A, Lefaucheur JP, Wang QP, et al. Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps. Arch Otolaryngol Head Neck Surg.1998.124(12):1361-6.
[57]Lloyd CM, Hawrylowicz CM. Regulatory T cells in asthma. Immunity. 2009,31(3):438-49.
[58]Moniuszko M, Bodzenta-Lukaszyk A, Dabrowska M. Oral glucocorticoid treatment decreases interleukin-10 receptor expression on peripheral blood leucocyte subsets. Clin Exp Immunol.2009,156(2):328-35. Epub 2009 Mar 9.
[59]Sun J, Madan R, Karp CL, et al. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med. 2009,15(3):277-84. Epub 2009 Feb 22.
[60]Oh JW, Seroogy CM, Meyer EH, et al. CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation. J Allergy Clin Immunol.2002,110(3):460-8.
[61]Till SJ, Francis JN, Nouri-Aria K, et al. Mechanisms of immunotherapy. J Allergy Clin Immunol.2004,113(6):1025-34; quiz 1035.
[62]Akdis M, Verhagen J, Taylor A, et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med. 2004,199(11):1567-75. Epub 2004 Jun 1.
[63]John M, Lim S, Seybold J, et al. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. Am J Respir Crit Care Med. 1998,157(1):256-62.
[64]Tournoy KG, Kips JC, Pauwels RA. Endogenous interleukin-10 suppresses allergen-induced airway inflammation and nonspecific airway responsiveness. Clin Exp Allergy.2000,30(6):775-83.
[65]Fu CL, Chuang YH, Chau LY, et al. Effects of adenovirus-expressing IL-10 in alleviating airway inflammation in asthma. J Gene Med. 2006,8(12):1393-9.
[66]Nouri-Aria KT, Wachholz PA, Francis JN, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol.2004,172(5):3252-9.
[67]KleinJan A, Dijkstra MD, Boks SS, et al. Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation. J Allergy Clin Immunol.1999,103(3 Pt 1):441-50.
[68]Chen YS, Arab SF, Westhofen M, et al. Expression of interleukin-5, interleukin-8, and interleukin-10 mRNA in the osteomeatal complex in nasal polyposis. Am J Rhinol.2005,19(2):117-23.
[69]Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science.2003,299(5609):1057-61. Epub 2003 Jan 9.
[70]Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet.2001,27(1):20-1.
[71]Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked:forkhead box protein 3 mutations and lack of regulatory T cells. J Allergy Clin Immunol.2007,120(4):744-50; quiz 751-2.
[72]Xu G, Mou Z, Jiang H, et al. A possible role of CD4+CD25+ T cells as well as transcription factor Foxp3 in the dysregulation of allergic rhinitis. Laryngoscope.2007,117(5):876-80.
[73]Li HB, Cai KM, Liu Z, et al. Foxp3+ T regulatory cells (Tregs) are increased in nasal polyps (NP) after treatment with intranasal steroid. Clin Immunol. 2008,129(3):394-400. Epub 2008 Sep 14.