Department of Rheumatology & Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China Department of Rheumatology & Immunology, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
Department of Rheumatology & Immunology, Clinical Immunology Center, Peking University People's Hospital, Beijing, China.
Ann Rheum Dis. 2015 Jun;74(6):1293-301. doi: 10.1136/annrheumdis-2013-204228. Epub 2014 Feb 12.
Regulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance.
Foxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test.
A higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA.
Increased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.
在正常和致病条件下，已经证实具有产生促炎性细胞因子 IL-17 能力的调节性 T 细胞（Treg）具有可塑性。然而，在自身免疫中，由于 Treg 向 Th17 的可塑性，IL-17 产生的 Treg 是否会失去其抑制功能仍不清楚。本研究旨在研究类风湿关节炎（RA）患者的 IL-17 产生 Treg，并对其调节能力和临床意义进行研究。
评估 RA 患者 CD4 T 淋巴细胞中 Foxp3 和 IL-17 的共表达。进行体外 T 细胞极化测定，以研究促炎细胞因子在 IL-17 产生 Treg 极化中的作用。通过体外抑制测定评估 IL-17 产生 Treg 在 RA 中的抑制功能。使用 Spearman 秩相关检验分析 RA 患者中该 Treg 亚群与临床特征之间的关系。
与健康受试者相比，RA 患者外周血中 IL-17 产生 Treg 的频率更高。这些来自外周血的细胞表现出 Th17 和 Treg 细胞的表型特征，并在体外抑制 T 细胞增殖。RA 滑液中的 Treg 失去了抑制功能。Treg 的 Th17 可塑性可由 IL-6 和 IL-23 诱导。该 Treg 亚群的比例增加与 RA 患者炎症标志物水平的降低相关，包括红细胞沉降率和 C 反应蛋白水平。
在 RA 患者中鉴定出高水平的 IL-17 产生 Treg。外周血中具有 Th17 可塑性的这种 Treg 亚群保留了抑制功能，并且与炎症程度较轻相关，这表明该 Treg 群体在 RA 中作为负调节剂起作用，但在 RA 滑膜部位可能具有致病性。
