c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis Academic Article uri icon

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 RORγt+ 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.

authors

  • Neumann, C
  • Blume, J
  • Roy, U
  • Teh, PP
  • Vasanthakumar, A
  • Beller, A
  • Liao, Yang
  • Heinrich, F
  • Arenzana, TL
  • Hackney, JA
  • Eidenschenk, C
  • Gálvez, EJC
  • Stehle, C
  • Heinz, GA
  • Maschmeyer, P
  • Sidwell, T
  • Hu, Y
  • Amsen, D
  • Romagnani, C
  • Chang, HD
  • Kruglov, A
  • Mashreghi, MF
  • Shi, Wei
  • Strowig, T
  • Rutz, S
  • Kallies, A
  • Scheffold, A

publication date

  • 2019