title: Distinct requirements for T-bet in gut innate lymphoid cells.
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.
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciumé
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Hayato
authors.initials: H
authors.lastname: Takahashi
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Alejandro V
authors.initials: AV
authors.lastname: Villarino
authors.forename: Kentner L
authors.initials: KL
authors.lastname: Singleton
authors.forename: Sean P
authors.initials: SP
authors.lastname: Spencer
authors.forename: Christoph
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Poholek
authors.forename: Golnaz
authors.initials: G
authors.lastname: Vahedi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D007113:Immunity, Innate / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor
chemical_list: D000950:Antigens, Ly; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D020825:T-Box Domain Proteins; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor; C118384:Ncr1 protein, mouse