T cell-intrinsic TLR2 stimulation promotes IL-10 expression and suppressive activity by CD45RbHi T cells
T cell-intrinsic TLR2 stimulation promotes IL-10 expression and suppressive activity by CD45RbHi T cells
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DOI：
10.1371/journal.pone.0180688
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发表时间：
2017-07-25
期刊：
影响因子：
3.7
通讯作者：
Cobb, Brian A.
中科院分区：
文献类型：
--
作者：
Jun, Janice C.;Jones, Mark B.;Cobb, Brian A.
toll样受体（Toll-like receptor, TLRs）是最具特征的先天免疫途径之一，但有证据表明，TLRs不仅局限于先天白细胞和一些上皮细胞，而且也在T细胞中表达。具体而言，已发表的关于FoxP3 +调节性T细胞的证据表明，它们表达功能性TLR2， TLR家族已经知道其与免疫抑制有关；然而，关于T细胞内在TLR2结合与细胞因子产生、T细胞分化或T细胞受体（TCR）刺激之间的关系知之甚少。在这里，我们证明了TCR和TLR2的共同刺激提供了T细胞的内在信号，产生了由IL-10主导的戏剧性的、协同的细胞因子反应。重要的是，在CD4(+) CD25（+）或CD4(+) FoxP3(+) Tregs中均未观察到这种反应，但导致抑制性CD4(+) CD25(+) CD62L(-) CD44(+) CD45Rb hi效应/记忆T细胞亚群的扩增，而这些T细胞亚群通常与免疫抑制无关。这项研究揭示了一种典型的先天免疫受体在效应/记忆T细胞中触发有效和抑制性IL-10反应的惊人能力，支持TLR2是T细胞上的共调节受体的观点。
While Toll-like receptors (TLRs) represent one of the best characterized innate immune pathways, evidence suggests that TLRs are not restricted to innate leukocytes and some epithelial cells, but are also expressed in T cells. Specifically, published evidence focusing on FoxP3 + regulatory T cells demonstrate that they express functional TLR2, which is already known among the TLR family for its association with immune suppression; however, little is known about the relationship between T cell-intrinsic TLR2 binding and cytokine production, T cell differentiation, or T cell receptor (TCR) stimulation. Here, we demonstrate that TCR and TLR2 co-stimulation provides a T cell-intrinsic signal which generates a dramatic, synergistic cytokine response dominated by IL-10. Importantly, the response was not seen in either CD4(+) CD25(+) or CD4(+) FoxP3(+) Tregs, yet resulted in the expansion of a suppressive CD4(+) CD25(+) CD62L(-) CD44(+) CD45Rb hi effector/memory T cell subset not typically associated with immune inhibition. This study reveals the striking ability of a prototypical innate immune receptor to trigger a potent and suppressive IL-10 response in effector/memory T cells, supporting the notion that TLR2 is a co-regulatory receptor on T cells.