Distinct requirements for T-bet in gut innate lymphoid cells

Giuseppe Sciumè, Kiyoshi Hirahara, Hayato Takahashi, Arian Laurence, Alejandro A. Villarino, Kentner L. Singleton, Sean P. Spencer, Christoph Wilhelm, Amanda C. Poholek, Golnaz Vahedi, Yuka Kanno, Yasmine Belkaid, John J. O'Shea

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)

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 reductionof 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 thesesubsets 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.

Original languageEnglish
Pages (from-to)2331-2338
Number of pages8
JournalJournal of Experimental Medicine
Volume209
Issue number13
DOIs
Publication statusPublished - 2012 Dec 17
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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