芳香烃受体在类风湿关节炎患者外周血CD4<sup>+</sup> CD25<sup>+</sup>T细胞的表达及意义

程琳; 钱龙; 谭悦; 李向培; 厉小梅; 汪国生

doi:10.16462/j.cnki.zhjbkz.2016.04.014

芳香烃受体在类风湿关节炎患者外周血CD4⁺ CD25⁺T细胞的表达及意义

doi: 10.16462/j.cnki.zhjbkz.2016.04.014

安徽医科大学附属安徽省立医院风湿免疫科, 安徽合肥 230001

基金项目:

中华医学会临床医学科研专项资金-风湿病学发展与研究资金（1204080038）

详细信息

作者简介:
程琳(1989-),女,安徽巢湖人,在读硕士研究生。主要研究方向:类风湿关节炎的发病机制。

中图分类号: R593.22
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出版历程
- 收稿日期: 2015-11-01
- 修回日期: 2016-01-20

Expression and significance of aryl hydrocarbon receptor in peripheral blood CD4⁺ CD25⁺T of rheumatoid arthritis

Department of Rheumatology and Immunology, Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, China

摘要

摘要: 目的以类风湿关节炎（rheumatoid arthritis，RA）患者为研究对象，观察芳香烃受体（aryl hydrocarbon receptor，AHR）在患者外周血CD4⁺CD25⁺T 细胞中的表达水平，探讨AHR在RA发病机制中的意义。方法采用流式细胞术检测RA患者（35例）及健康对照组（14例）中AHR 阳性细胞在外周血CD4⁺CD25⁺T 及CCR6⁺CD4⁺T细胞中所占比例，并将所得结果与患者临床指标的相关性做分析。结果 RA 组外周血CD4⁺CD25⁺T细胞中AHR 阳性细胞所占比例为（17.90（6.10，80.10））%，低于健康对照组（52.43（19.18，96.43））%，差异有统计学意义（Z=-4.362，P<0.001）；正常对照组外周血CD4⁺CD25⁺T细胞中AHR阳性细胞比例为（52.49±19.18）%，高于CCR6⁺CD4⁺T细胞中（23.18±5.62）%，且都高于外周血单个核细胞（peripheral blood mononuclear cells，PBMCs）中（18.06±7.80）%，三组间差异有统计学意义（χ²=24.03，P<0.001）；RA组CD4⁺CD25⁺T细胞中的AHR比例为（17.90（6.10，80.10））%，低于PBMCs中的（34.43（8.72，56.37））%，且都低于CCR6⁺CD4⁺T细胞中的（46.15（20.18，87.31））%，三组间差异有统计学意义（χ²=38.29，P<0.001）。结论 RA外周血CD4⁺CD25⁺T细胞中，AHR 阳性细胞比例降低，而在CCR6⁺CD4⁺T细胞中升高，AHR可能通过调节辅助性T细胞17与调节性T细胞细胞的分化，影响Th17与Treg之间的平衡，从而参与RA的发病机制。
- 关节炎,类风湿 /
- 受体,芳香烃 /
- T淋巴细胞
Abstract: Objective To explore the significance of aryl hydrocarbon receptor (AHR) in the pathogenesis of rheumatoid arthritis(RA) by detecting the percentage of AHR positive in CD4⁺ CD25⁺T cells. Methods Peripheral blood of 35 patients with RA and 14 healthy controls were collected. Flow cytometry (FCM) technology was applied to detect the proportion of CD4⁺ CD25⁺T cells and AHR positive cells in peripheral blood of each individual and the percentage of AHR positive cells in CCR6⁺CD4⁺T cells were also tested. Clinical data was recorded in detail and disease activity score in 28 joints (DAS28 ) was calculated. Then, the association between the percentage of AHR positive cells in CD4⁺ CD25⁺T cells and clinical data was analyzed. Results In peripheral blood of RA patients, the percentage of AHR positive cells in CD4⁺CD25⁺T cells was significantly lower than that in healthy controls ((17.90(6.10,80.10))% vs.(52.43(19.18,96.43))%,Z=-4.362,P<0.001); In peripheral blood of healthy controls, the percentage of AHR positive cells in CD4⁺CD25⁺T cells was significantly higher than that in CCR6⁺CD4⁺Tcells, and was also significantly higher than that in peripheral blood mononuclear cells(PBMCs) ((52.49±19.18)% vs. (23.18±5.62)% vs. (18.06±7.80)%, χ²=24.03, P<0.001); In peripheral blood of RA patients, the percentage of AHR positive cells in CD4⁺CD25⁺T cells was significantly lower than that in CCR6⁺CD4⁺T cells, and was also significantly lower than that in PBMCs((17.90(6.10,80.10))% vs. ((46.15(20.18,87.31))%vs. (34.43(8.72,56.37))%, χ²=38.29, P<0.001); Nevertheless, no statistically significant correlation was found between clinical data and the percentage of AHR positive cells in CD4⁺ CD25⁺T cells. Conclusions AHR may participate in the pathogenesis of RA by controlling the differentiation of Th17 and Treg cells .
- Arthritis,rheumatoid /
- Receptors,aryl hydrocarbon /
- T-lymphocytes

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参考文献(19)

Nguyen NT, Nakahama T, Kishimoto T, et al. Aryl hydrocarbon receptor and experimental autoimmune arthritis [J]. Semin Immunopathol, 2013,35(6):637-644.

Frericks M, Meissner M, Esser C. Microarray analysis of the AHR system:tissue-specific flexibility in and target genes [J]. Toxicol Appl Pharmacol, 2007,220(3):320-332.

Hill JA, Feuerer M, Tash K, et al. Foxp3 transcription-factor-dependent and independent regulation of the regulatory T cell transcriptional signature [J]. Immunity, 2007,27(5):786-800.

Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance [J]. Cell, 2008,133(5):775-787.

Singh NP, Singh UP, Singh B, et al. Activation of aryl hydrocarbon receptor (AHR) leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis [J]. PLoS One, 2011,6(8):e23522.

Denison MS, Nagy SR. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals [J]. Annu Rev Pharmacol Toxicol, 2003,43:309-334.

Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis [J]. Lancet, 2009,373(9664):659-672.

Nakahama T, Kimura A, Nguyen NT, et al. Aryl hydrocarbon receptor deficiency in T cells suppresses the development of collagen-induced arthritis [J]. Proc Natl Acad Sci USA, 2011,108(34):14222-14227.

Quintana FJ, Basso AS, Lglesias AH, et al. Control of Treg and Th17 cell differentiation by the aryl hydrocarbon receptor [J]. Nature, 2008,453(7191):65-71.

Hirota K, Yoshitomi H, Hashimoto M, et al. Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model [J]. J Exp Med, 2007,204(12):2803-2812.

Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells [J]. J Exp Med, 2007,204(8):1849-1861.

Singh SP, Zhang HH, Foley JF, et al. Human T cells that are able to produce IL-17 express the chemokine receptor CCR6 [J]. J Immunol, 2008,180(1):214-221.

Kerkvliet NI, Steppan LB, Vorachek W, et al. Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+T cells in pancreatic lymph nodes [J]. Immunotherapy, 2009,1(4):539-547.

Kimura A, Kishimoto T. Thl7 cells in inflammation [J]. Int Immunopharmacol, 2011,11(3):319-322.

de Kleer IM, Wedderburn LR, Taams LS, et al. CD4⁺CD25 bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis [J]. Immunol, 2004,172(10):6435-6443.

Ehrenstein MR, Evans JG, Singh A, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy [J]. J Exp Med, 2004,200(3):277-285.

Valencia X, Stephens G, Goldbach-Mansky R, et al. TNF down-modulates the function of human CD4⁺CD25hi T-regulatory cells [J]. Blood, 2006,108(1):253-261.

Nguyen LT, Jacobs J, Mathis D, et al. Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis [J]. Arthritis Rheum, 2007,56(2):509-520.

谭悦,钱龙,李向培,等. 芳香烃受体在类风湿关节炎患者外周血CCR6⁺CD4⁺ T细胞的表达及意义 [J]. 免疫学杂志, 2014,7(30):612-616.

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芳香烃受体在类风湿关节炎患者外周血CD4⁺ CD25⁺T细胞的表达及意义

doi: 10.16462/j.cnki.zhjbkz.2016.04.014

作者简介:
程琳(1989-),女,安徽巢湖人,在读硕士研究生。主要研究方向:类风湿关节炎的发病机制。

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Expression and significance of aryl hydrocarbon receptor in peripheral blood CD4⁺ CD25⁺T of rheumatoid arthritis

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芳香烃受体在类风湿关节炎患者外周血CD4+ CD25+T细胞的表达及意义

doi: 10.16462/j.cnki.zhjbkz.2016.04.014

作者简介: 程琳(1989-),女,安徽巢湖人,在读硕士研究生。主要研究方向:类风湿关节炎的发病机制。

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出版历程

Expression and significance of aryl hydrocarbon receptor in peripheral blood CD4+ CD25+T of rheumatoid arthritis

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出版历程

目录

芳香烃受体在类风湿关节炎患者外周血CD4⁺ CD25⁺T细胞的表达及意义

作者简介:
程琳(1989-),女,安徽巢湖人,在读硕士研究生。主要研究方向:类风湿关节炎的发病机制。

Expression and significance of aryl hydrocarbon receptor in peripheral blood CD4⁺ CD25⁺T of rheumatoid arthritis