MUCOSAL IMMUNOLOGY. The microbiota regulates type 2 immunity through RORγt⁺ T cells

Science. 2015 Aug 28;349(6251):989-93. doi: 10.1126/science.aac4263. Epub 2015 Jul 9.

Abstract

Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (T(H)17) cells and regulatory T cells (T(regs)) in the intestine. Here, we report that microbiota-induced T(regs) express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to T(H)17 cells. In the absence of RORγt(+) T(regs), T(H)2-driven defense against helminths is more efficient, whereas T(H)2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt(+) T(regs) and T(H)17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis, Ulcerative / immunology
  • Colon / immunology
  • Colon / microbiology
  • Germ-Free Life
  • Homeostasis
  • Immunity, Mucosal*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Intestine, Small / immunology
  • Intestine, Small / microbiology
  • Intestines / immunology
  • Intestines / microbiology*
  • Mice
  • Microbiota / immunology*
  • Models, Immunological
  • Nematospiroides dubius
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
  • Specific Pathogen-Free Organisms
  • Strongylida Infections / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Vitamin A / metabolism

Substances

  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse
  • Vitamin A