APRIL Induces a Novel Subset of IgA+ Regulatory B Cells That Suppress Inflammation via Expression of IL-10 and PD-L1
APRIL Induces a Novel Subset of IgA+ Regulatory B Cells That Suppress Inflammation via Expression of IL-10 and PD-L1
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DOI：
10.3389/fimmu.2019.01368
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发表时间：
2019-06-14
影响因子：
7.3
通讯作者：
Baeten, Dominique L. P.
中科院分区：
文献类型：
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作者：
Fehres, Cynthia M.;van Uden, Nathalie O.;Baeten, Dominique L. P.
调节性B细胞（BCRs）是通过多种机制调节免疫应答的免疫抑制细胞。这些细胞的分化和活化所需的信号仍然知之甚少。我们已经证明过表达A促增殖诱导配体（APRIL）可以降低小鼠胶原诱导性关节炎（CIA）的发病率和严重程度。此外，我们已经描述了APRIL，而不是BAFF，促进人B细胞中IL-10的产生和调节功能。因此，我们假设APRIL而不是BAFF可能参与诱导和/或激活产生IL-10的抑制体外和体内炎症反应的BCLs。在这里，我们描述了APRIL促进幼稚人B细胞分化为产生IL-10的伊加（+）B细胞。这些APRIL诱导的伊加（+）B细胞显示出布雷格表型，并通过IL-10和PD-L1抑制T细胞和巨噬细胞应答。此外，APRIL诱导的产生IL-10的BELINE在实验性自身免疫性脑炎（EAE）和接触性超敏反应（CHS）模型中抑制体内炎症。最后，我们发现APRIL和IL-10在炎性关节炎患者的炎症滑膜组织中有很强的相关性。总的来说，这些观察结果表明这种新型APRIL诱导的伊加（+）布雷格群体与免疫稳态和免疫病理学的潜在相关性。
Regulatory B cells (Bregs) are immunosuppressive cells that modulate immune responses through multiple mechanisms. The signals required for the differentiation and activation of these cells remain still poorly understood. We have already shown that overexpression of A PRoliferation-Inducing Ligand (APRIL) reduces the incidence and severity of collagen-induced arthritis (CIA) in mice. Furthermore, we have described that APRIL, but not BAFF, promoted IL-10 production and regulatory functions in human B cells. Therefore, we hypothesized that APRIL, but not BAFF, may be involved in the induction and/or activation of IL-10 producing Bregs that suppress inflammatory responses in vitro and in vivo. Here, we describe that APRIL promotes the differentiation of naive human B cells to IL-10-producing IgA(+) B cells. These APRIL-induced IgA(+) B cells display a Breg phenotype and inhibit T cell and macrophage responses through IL-10 and PD-L1. Moreover, APRIL-induced IL-10 producing Bregs suppress inflammation in vivo in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models. Finally, we showed a strong correlation between APRIL and IL-10 in the inflamed synovial tissue of inflammatory arthritis patients. Collectively, these observations indicate the potential relevance of this novel APRIL-induced IgA(+) Breg population for immune homeostasis and immunopathology.