Cell Reports
Volume 21, Issue 7, 14 November 2017, Pages 1853-1869
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Article
Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance

https://doi.org/10.1016/j.celrep.2017.10.090Get rights and content
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Highlights

  • Expression of IL-35 and IL-10 defines two distinct subsets of Treg effectors

  • IL-35-Tregs and IL-10-Tregs have different transcription factor dependency

  • IL-35-Tregs and IL-10-Tregs have different activation status and geographic locations

  • IL-35-Tregs and IL-10-Tregs cooperate to maintain immune tolerance

Summary

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.

Keywords

effector Treg
interleukin 35
interleukin 10
Blimp1
Foxp3

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