Gata3 drives development of RORγt+ group 3 innate lymphoid cells

J Exp Med. 2014 Feb 10;211(2):199-208. doi: 10.1084/jem.20131038. Epub 2014 Jan 13.

Abstract

Group 3 innate lymphoid cells (ILC3) include IL-22-producing NKp46(+) cells and IL-17A/IL-22-producing CD4(+) lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt(+) ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt(+) ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Citrobacter rodentium
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Enterobacteriaceae Infections / immunology
  • Female
  • Fetal Development / immunology
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology*
  • Immunity, Innate*
  • Immunity, Mucosal
  • Interleukin-22
  • Interleukins / metabolism
  • Liver / cytology
  • Liver / embryology
  • Liver / immunology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Pregnancy

Substances

  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rag2 protein, mouse
  • Rorc protein, mouse