T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells

Front Immunol. 2021 Feb 2:11:623324. doi: 10.3389/fimmu.2020.623324. eCollection 2020.


Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an in vivo fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.

Keywords: ILCs; T-bet; innate lymphoid cells; intestinal inflammation; mucosal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / pathology
  • Immunity, Innate*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Lymphocytes / immunology*
  • Lymphocytes / pathology
  • Mice
  • Mice, Knockout
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*


  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Interleukin-7
  • Rorc protein, mouse
  • STAT1 Transcription Factor
  • STAT4 Transcription Factor
  • Stat1 protein, mouse
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21