title: Gata3 drives development of RORγt+ group 3 innate lymphoid cells.
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.
authors.affiliation: Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serafini
authors.forename: Roel G J
authors.initials: RG
authors.lastname: Klein Wolterink
authors.forename: Naoko
authors.initials: N
authors.lastname: Satoh-Takayama
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Christian A J
authors.initials: CA
authors.lastname: Vosshenrich
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D044082:Citrobacter rodentium; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology; D005260:Female; D047109:Fetal Development / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007378:Interleukins / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D000097043:Interleukin-22
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000097043:Interleukin-22; C494748:Gata3 protein, mouse; C499308:Rag2 protein, mouse; C539901:Rorc protein, mouse