Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance
Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance
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IL-35 和 IL-10 的相互表达定义了维持免疫耐受所需的两个不同的效应 Treg 子集。
DOI：
10.1016/j.celrep.2017.10.090
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发表时间：
2017-11-14
期刊：
影响因子：
8.8
通讯作者：
Zhou, Xuyu
中科院分区：
文献类型：
--
作者：
Wei, Xundong;Zhang, Jianhua;Zhou, Xuyu
调节性T细胞（TCRs）可以通过多种抑制机制发挥其功能;然而，目前还不清楚TCRs如何确切地利用这些机制。在这项研究中，我们发现，白细胞介素-35（IL-35）产生的T细胞是一个独特的效应人口从IL-10产生的子集。我们还发现，这两个亚群的效应TcR具有不同的转录因子依赖性。终末分化调节因子Blimp 1仅对IL-10的产生至关重要，但对IL-35不重要; Foxp 3对IL-35至关重要，但对IL-10的产生至关重要。此外，我们证明了IL-35产生和IL-10产生Tcls具有不同的激活状态，在次级淋巴器官中不具有相同的地理位置，并且以互补的方式工作以防止自身免疫。因此，我们的研究强调了效应Treg生成的重要性。我们还提供了Treg激活状态调节不同效应Treg亚群的产生的证据，这些亚群协同工作以维持免疫耐受。
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production. Furthermore, we demonstrated that IL-35-producing and IL-10-producing Tregs have a different activation status, do not share the same geographic locations in secondary lymphoid organs, and work in a complementary way to prevent autoimmunity. Thus, our study highlights the importance of effector Treg generation. We also provide evidence of Treg activation status tuning the generation of distinct effector Treg subsets, which work cooperatively to maintain immune tolerance.