Distinct requirements for T-bet in gut innate lymphoid cells

J Exp Med. 2012 Dec 17;209(13):2331-8. doi: 10.1084/jem.20122097. Epub 2012 Dec 3.

Abstract

Interleukin (IL)-22-producing innate lymphoid cells (ILCs; ILC22) comprise a heterogeneous population of cells that are dependent on the transcription factor retinoid-related orphan γt (RORγt) and are critical for barrier function of the intestinal mucosa. A distinct ILC22 subset expresses the natural cytotoxicity receptor NKp46 (NKp46+ ILC22); however, the factors that contribute to the generation of this population versus other subsets are largely unknown. Herein, we show that T-bet (encoded by Tbx21) was highly expressed in NKp46+ ILC22, a feature shared by all NKp46+ cells present in the intestine but not by other IL-22-producing populations. Accordingly, the absence of T-bet resulted in loss of NKp46+ ILC22 in the intestinal lamina propria. The residual NKp46+ ILC22 present in Tbx21(-/-) mice showed a marked reduction of Rorγt expression and impairment in IL-22 production. Generation and functions of gut NK1.1+ cells were also altered. Bone marrow chimera experiments revealed a cell-intrinsic requirement for T-bet in these subsets and competitive reconstitution experiments revealed roles for T-bet in multiple ILC subsets. Thus, T-bet has a general importance for ILC in the gut and plays a selective and critical role in the generation of NKp46+ ILC22.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Gene Expression
  • Immunity, Innate* / genetics
  • Interleukin-22
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Interleukins / biosynthesis
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • T-Box Domain Proteins / deficiency
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-bet Transcription Factor

Substances

  • Antigens, Ly
  • Interleukin-7 Receptor alpha Subunit
  • Interleukins
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • T-Box Domain Proteins
  • T-bet Transcription Factor