Chemerin/chemR23对银屑病患者外周血Th9/Treg细胞平衡的影响
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摘要
目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外周血中CD4+T细胞,行实时RT-PCR和ELISA检测细胞中chemerin和其受体chemR23的表达;用不同浓度的chemerin(50,100,150,200 ng/mL)分别处理从健康志愿者外周血分离得到的CD4+T细胞,行MT T比色法检测细胞活力以筛选最适浓度;采用ELISA检测炎性细胞因子水平;行流式细胞术检测Th9和Treg细胞数。结果:与对照相比,银屑病患者外周血中chemerin和chemR23的表达均显著增加,T h 9/Treg比例明显上升(均P<0.05);选取最适浓度150 ng/mL的chemerin处理CD4+T细胞后,细胞中白细胞介素(IL)-6,IL-9和IL-17的水平均显著增加,Th9/Treg比例明显上升(均P<0.05),而chemR23沉默可反转chemerin对CD4+T细胞的上述作用(均P<0.05)。结论:Chemerin通过chemR23调节银屑病患者外周血CD4+T淋巴细胞中的T h 9/Treg细胞免疫平衡。
Objective: To investigate the effects of chemerin on helper T cells 9(Th 9)/regulatory T cells(Treg) in patients with psoriasis and the potential molecular mechanisms.Methods: Twenty-five patients with psoriasis and twenty health y volunteers were selected for th is study. CD4+ T cells were isolated from peripheral blood of samples by magnetic bead separation. Th e levels of chemerin and its receptor chemR23 were detected by real-time RT-PCR and ELISA. CD4+ T cells isolated from the health y volunteers were treated with different concentrations of chemerin(50, 100, 150, 200 ng/mL), then cell viability was detected by MTT assay. Th e expression of inflammatory molecules and Th 9/Treg were detected by ELISA and flow cytometry, respectively.Results: The expressions of chemerin and chemR23 in peripheral blood from patients with psoriasis were higher th an those in health y control(both P<0.05). The Th9/Treg was higher in patients with psoriasis th an th at in health y control(P<0.05). After treating CD4+ T cells with 150 ng/mL of chemerin, the levels of IL-6, IL-9 and IL-17 were increased significantly(all P<0.05). Additionally, Th9/Treg was increased(P<0.05) and the cell balance was disrupt. However, the effects of chemerin on CD4+ T cells were reversed by silencing of chemR23(all P<0.05).Conclusion: Chemerin may regulate the immune balance for Th9/Treg in CD4+ T cells from patients of psoriasis.
Objective: To investigate the effects of chemerin on helper T cells 9(Th 9)/regulatory T cells(Treg) in patients with psoriasis and the potential molecular mechanisms.Methods: Twenty-five patients with psoriasis and twenty health y volunteers were selected for th is study. CD4+ T cells were isolated from peripheral blood of samples by magnetic bead separation. Th e levels of chemerin and its receptor chemR23 were detected by real-time RT-PCR and ELISA. CD4+ T cells isolated from the health y volunteers were treated with different concentrations of chemerin(50, 100, 150, 200 ng/mL), then cell viability was detected by MTT assay. Th e expression of inflammatory molecules and Th 9/Treg were detected by ELISA and flow cytometry, respectively.Results: The expressions of chemerin and chemR23 in peripheral blood from patients with psoriasis were higher th an those in health y control(both P<0.05). The Th9/Treg was higher in patients with psoriasis th an th at in health y control(P<0.05). After treating CD4+ T cells with 150 ng/mL of chemerin, the levels of IL-6, IL-9 and IL-17 were increased significantly(all P<0.05). Additionally, Th9/Treg was increased(P<0.05) and the cell balance was disrupt. However, the effects of chemerin on CD4+ T cells were reversed by silencing of chemR23(all P<0.05).Conclusion: Chemerin may regulate the immune balance for Th9/Treg in CD4+ T cells from patients of psoriasis.
引文
[1]Martini S, Pozzi G, Carubbi C, et al. PKCεpromotes human Th17differentiation:Implications in the path ophysiology of psoriasis[J].Eur J Immunol, 2018, 48(4):644-654.
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[3]Harusato A, Abo H, Ngo VL, et al. IL-36gamma signaling controlstheinducedregulatoryTcell-Th9cellbalanceviaNFkappaBactivation and STAT transcription factors[J]. Mucosal Immunol,2017, 10(6):1455-1467.
[4]SchlapbachC,GehadA,YangC,etal.HumanTH9cellsareskin-tropicandhaveautocrineandparacrineproinflammatorycapacity[J]. Sci Transl Med, 2014, 6(219):219ra218.
[5]罗权,林玲,赵恬,等. Chemerin在寻常性银屑病患者血清中的表达水平及意义[J].中国中西医结合皮肤性病学杂志, 2014,13(4):210-212.LUO Quan, LIN Ling, ZHAO Tian, et al. Detection of serum levelsof Chemerin in patients with psoriasis vulgaris[J]. Chinese JournalofDermatovenereologyofIntegratedTraditionalandWesternMedicine, 2014, 13(4):210-212.
[6]Topic I, Simic D. Prevalence of metabolic syndrome in patients with psoriasis at Mostar Clinical Hospital[J]. Acta Clin Croat, 2013,52(1):53-58.
[7]Ommen P, Stjernholm T, Kragstrup T, et al. The role of leptin inpsoriasiscomprisesaproinflammatoryresponsebythedermalfibroblast[J]. Br J Dermatol, 2016, 174(1):187-190.
[8]Shibata S, Tada Y, Hau CS, et al. Adiponectin regulates psoriasiformskininflammationbysuppressingIL-17productionfromgammadelta-T cells[J]. Nat Commun, 2015, 6:7687.
[9]Hau CS, Kanda N, Noda S, et al. Visfatin enhances the production ofcathelicidin antimicrobial peptide, human beta-defensin-2, humanbeta-defensin-3,andS100A7inhumankeratinocytesandtheirorth ologs in murine imiquimod-induced psoriatic skin[J]. Am JPath ol, 2013, 182(5):1705-1717.
[10]Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling,andphysiologicalfunctionofchemerin[J].IUBMBLife,2014,66(1):19-26.
[11]Banas M, Zabieglo K, Kasetty G, et al. Chemerin is an antimicrobialagent in human epidermis[J]. PLoS One, 2013, 8(3):e58709.
[12]Mariani F, Roncucci L. Chemerin/chemR23 axis in inflammationonset and resolution[J]. Inflamm Res, 2015, 64(2):85-95.
[13]Zhang P, Chen HX, Duan YQ, et al. Analysis of Th1/Th2 responsepatternforeryth rodermicpsoriasis[J].JHuazhongUnivSciTechnolog Med Sci, 2014, 34(4):596-601.
[14]Piaserico S, Sandini E, Saldan A, et al. Effects of TNF-alpha inhibitorson circulating Th17 cells in patients affected by severe psoriasis[J].Drug Dev Res, 2014, 75(Suppl 1):S73-76.
[15]Kagami S, Rizzo HL, Kurtz SE, et al. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense againstCandida albicans[J]. J Immunol, 2010, 185(9):5453-5462.
[16]Dardalhon V, Awasth i A, Kwon H, et al. IL-4 inhibits TGF-beta-induced Foxp3+T cells and, together with TGF-beta, generates IL-9+IL-10+Foxp3(–)effector T cells[J]. Nat Immunol, 2008, 9(12):1347-1355.
[2]ButtrickTS,WangW,YungC,etal.Foxo1promotesTh9celldifferentiation and airway allergy[J]. Sci Rep, 2018, 8(1):818.
[3]Harusato A, Abo H, Ngo VL, et al. IL-36gamma signaling controlstheinducedregulatoryTcell-Th9cellbalanceviaNFkappaBactivation and STAT transcription factors[J]. Mucosal Immunol,2017, 10(6):1455-1467.
[4]SchlapbachC,GehadA,YangC,etal.HumanTH9cellsareskin-tropicandhaveautocrineandparacrineproinflammatorycapacity[J]. Sci Transl Med, 2014, 6(219):219ra218.
[5]罗权,林玲,赵恬,等. Chemerin在寻常性银屑病患者血清中的表达水平及意义[J].中国中西医结合皮肤性病学杂志, 2014,13(4):210-212.LUO Quan, LIN Ling, ZHAO Tian, et al. Detection of serum levelsof Chemerin in patients with psoriasis vulgaris[J]. Chinese JournalofDermatovenereologyofIntegratedTraditionalandWesternMedicine, 2014, 13(4):210-212.
[6]Topic I, Simic D. Prevalence of metabolic syndrome in patients with psoriasis at Mostar Clinical Hospital[J]. Acta Clin Croat, 2013,52(1):53-58.
[7]Ommen P, Stjernholm T, Kragstrup T, et al. The role of leptin inpsoriasiscomprisesaproinflammatoryresponsebythedermalfibroblast[J]. Br J Dermatol, 2016, 174(1):187-190.
[8]Shibata S, Tada Y, Hau CS, et al. Adiponectin regulates psoriasiformskininflammationbysuppressingIL-17productionfromgammadelta-T cells[J]. Nat Commun, 2015, 6:7687.
[9]Hau CS, Kanda N, Noda S, et al. Visfatin enhances the production ofcathelicidin antimicrobial peptide, human beta-defensin-2, humanbeta-defensin-3,andS100A7inhumankeratinocytesandtheirorth ologs in murine imiquimod-induced psoriatic skin[J]. Am JPath ol, 2013, 182(5):1705-1717.
[10]Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling,andphysiologicalfunctionofchemerin[J].IUBMBLife,2014,66(1):19-26.
[11]Banas M, Zabieglo K, Kasetty G, et al. Chemerin is an antimicrobialagent in human epidermis[J]. PLoS One, 2013, 8(3):e58709.
[12]Mariani F, Roncucci L. Chemerin/chemR23 axis in inflammationonset and resolution[J]. Inflamm Res, 2015, 64(2):85-95.
[13]Zhang P, Chen HX, Duan YQ, et al. Analysis of Th1/Th2 responsepatternforeryth rodermicpsoriasis[J].JHuazhongUnivSciTechnolog Med Sci, 2014, 34(4):596-601.
[14]Piaserico S, Sandini E, Saldan A, et al. Effects of TNF-alpha inhibitorson circulating Th17 cells in patients affected by severe psoriasis[J].Drug Dev Res, 2014, 75(Suppl 1):S73-76.
[15]Kagami S, Rizzo HL, Kurtz SE, et al. IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense againstCandida albicans[J]. J Immunol, 2010, 185(9):5453-5462.
[16]Dardalhon V, Awasth i A, Kwon H, et al. IL-4 inhibits TGF-beta-induced Foxp3+T cells and, together with TGF-beta, generates IL-9+IL-10+Foxp3(–)effector T cells[J]. Nat Immunol, 2008, 9(12):1347-1355.