Montpellier University, Montpellier, France.
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
Front Immunol. 2018 May 3;9:961. doi: 10.3389/fimmu.2018.00961. eCollection 2018.
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10 cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10 cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts. B10 cells from HC did not decrease T helper 1 (Th1) nor and tumor necrosis factor α producing T cell (TNFα T cell) differentiation. We showed that in RA, B10 cells could also induce Treg cells and Tr1 from naïve T cells. Contrary to HC, B10 cells from RA patients increased naïve T cell conversion into Th1. Interestingly, PD-L2, a programmed death-1 (PD-1) ligand that inhibits PD-L1 and promotes Th1 differentiation, was overexpressed on RA B10 cells compared to HC B10 cells. Together, our findings showed that CpG-induced B10 cells may be used to increase Treg cells in patients with RA. However, CpG may not be the most adequate stimuli as CpG-induced B10 cells also increased inflammatory T cells in those patients.
尽管越来越多的证据强调了增加产生白细胞介素 10 的 B 细胞（B10 细胞）在自身免疫性疾病中的相关性，但它们在患者中的功能仍不清楚。本研究旨在评估从健康对照（HC）和类风湿关节炎（RA）患者中分离出的 CpG 诱导的 B10 细胞对幼稚 T 细胞分化的功能。我们证明，来自 HC 的 CpG 诱导的 B10 细胞通过分泌白细胞介素 10 和细胞接触，驱动幼稚 T 细胞向调节性 T 细胞（Treg 细胞）和产生白细胞介素 10 的 T 细胞（Tr1）分化。HC 的 B10 细胞不会减少辅助性 T 细胞 1（Th1）和肿瘤坏死因子 α 产生的 T 细胞（TNFα T 细胞）分化。我们表明，在 RA 中，B10 细胞也可以从幼稚 T 细胞诱导 Treg 细胞和 Tr1。与 HC 不同，RA 患者的 B10 细胞可以增加幼稚 T 细胞向 Th1 的转化。有趣的是，程序性死亡配体 2（PD-L2），一种抑制 PD-L1 并促进 Th1 分化的程序性死亡受体 1（PD-1）配体，在 RA B10 细胞上的表达高于 HC B10 细胞。总之，我们的研究结果表明，CpG 诱导的 B10 细胞可用于增加 RA 患者的 Treg 细胞。然而，CpG 可能不是最合适的刺激物，因为 CpG 诱导的 B10 细胞也增加了这些患者中炎症性 T 细胞的数量。
