An imbalance between blood CD4+CXCR5+Foxp3+ Tfr cells and CD4+CXCR5+Tfh cells may contribute to the immunopathogenesis of rheumatoid arthritis
An imbalance between blood CD4+CXCR5+Foxp3+ Tfr cells and CD4+CXCR5+Tfh cells may contribute to the immunopathogenesis of rheumatoid arthritis
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血液CD4( )CXCR5( )Foxp3( ) Tfr细胞和CD4( )CXCR5( )Tfh细胞之间的不平衡可能导致类风湿性关节炎的免疫发病机制
DOI：
10.1016/j.molimm.2020.06.003
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发表时间：
2020-09-01
影响因子：
3.6
通讯作者：
Zhang, Yanli
中科院分区：
文献类型：
--
作者：
Cao, Gan;Wang, Peipei;Zhang, Yanli
背景：滤泡辅助T（Tfh）细胞是活化的CD4（+）T细胞的一个亚群，可以协助生发中心的形成和维持。滤泡调节性 T (Tfr) 细胞是一类新型调节性 T 细胞，在抑制体液免疫细胞中发挥重要作用。与Tfh细胞的作用相反，Tfr细胞可以抑制Tfh细胞和B细胞的功能。血液 Tfr/Tfh 比率失衡导致自身反应性 B 细胞扩增和自身抗体产生 ()。然而，Tfr细胞和Tfh细胞在RA（类风湿性关节炎）发病机制中的作用尚不清楚。本研究的目的是探讨Tfr细胞和Tfh细胞在RA发病机制中的功能。方法：我们招募了20名符合美国风湿病学会诊断标准的患者和20名健康对照（HC）。采用流式细胞仪分析20例RA患者CD4(+)CXCR5(+)Foxp3(+)Tfr细胞和CD4(+)CXCR5(+)Tfh细胞的数量。此外，还评估了 Tfr/Tfh 比值与特征性临床参数之间的相关性。通过ELISA测定血清IL-21（白细胞介素21）、CXCL13（趋化因子（C-X-C基序）配体13）和TGF-β（转化生长因子-β）的水平。 H&E染色检测滑膜异位生发中心(GC)的形成。还分析了 CXCR5（C-X-C 趋化因子受体 5 型）、CXCL13、ICOS（诱导型共刺激剂）和 TGF-β mRNA 的转录水平。另外，采用免疫组化法检测滑膜中Bcl-6（B细胞淋巴瘤6）、CXCR5、CXCL13、ICOS的表达。结果：RA患者外周血中Tfh细胞较多，反之，血中Tfr细胞频率（p
Background: Follicular helper T (Tfh) cells are a subgroup of activated CD4(+) T cells which can assist the formation and maintenance of germinal centers. Follicular regulatory T (Tfr) cells are a new class of regulatory T cells which play a major role in suppressing cells in humoral immunity. In contrast to the role of Tfh cells, Tfr cells can inhibit the function of Tfh cells and B cells. Imbalance of blood Tfr/Tfh ratio resulted in the expansion of auto-reactive B cells and auto-antibody production (). However, the effect of Tfr cells and Tfh cells in the pathogenesis of RA (rheumatoid arthritis) is unclear. The purpose of this study was to investigate the function of Tfr cells and Tfh cells in the pathogenesis of RA.Methods: We recruited 20 patients fulfilled the the American College of Rheumatology diagnosis criteria and 20 healthy controls (HCs). The number of CD4(+)CXCR5(+)Foxp3(+) Tfr cells and CD4(+)CXCR5(+) Tfh cells in 20 RA patients were measured by flow cytometry analysis. Furthermore, the correlations between the Tfr/Tfh ratio and the characteristic clinical parameters were assessed. The serum levels of IL-21(interleukin-21), CXCL13 (chemokine (C-X-C motif) ligand 13) and TGF-beta (Transforming growth factor-beta) were measured by ELISA. The formation of ectopic germinal center (GC) of synovial membrane was examined by H&E staining. The transcriptional levels of CXCR5 (C-X-C chemokine receptor type 5), CXCL13, ICOS (inducible co-stimulater) and TGF-beta mRNA were also analyzed. In addition, the expression of Bcl-6 (B-cell lymphoma 6), CXCR5, CXCL13 and ICOS in synovial membrane were examined by immunohistochemistry.Results: RA patients had more Tfh cells in peripheral blood, conversely, the frequency of blood Tfr cells (p