c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis
Journal Title
Nature Immunology
Publication Type
Journal Article in press
Abstract
Foxp3(+) regulatory T cells (Treg cells) are crucial for the maintenance of immune homeostasis both in lymphoid tissues and in non-lymphoid tissues. Here we demonstrate that the ability of intestinal Treg cells to constrain microbiota-dependent interleukin (IL)-17-producing helper T cell (TH17 cell) and immunoglobulin A responses critically required expression of the transcription factor c-Maf. The terminal differentiation and function of several intestinal Treg cell populations, including RORgammat(+) Treg cells and follicular regulatory T cells, were c-Maf dependent. c-Maf controlled Treg cell-derived IL-10 production and prevented excessive signaling via the kinases PI(3)K (phosphatidylinositol-3-OH kinase) and Akt and the metabolic checkpoint kinase complex mTORC1 (mammalian target of rapamycin) and expression of inflammatory cytokines in intestinal Treg cells. c-Maf deficiency in Treg cells led to profound dysbiosis of the intestinal microbiota, which when transferred to germ-free mice was sufficient to induce exacerbated intestinal TH17 responses, even in a c-Maf-competent environment. Thus, c-Maf acts to preserve the identity and function of intestinal Treg cells, which is essential for the establishment of host-microbe symbiosis.
Publisher
Springer Nature
WEHI Research Division(s)
Bioinformatics
PubMed ID
30778241
NHMRC Grants
NHMRC/1069075 NHMRC/1106378
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-03-13 11:54:09
Last Modified: 2019-03-13 01:54:20
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