title: Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells.
abstract: Group 2 innate lymphoid cells (ILC2s; also called nuocytes, innate helper cells, or natural helper cells) provide protective immunity during helminth infection and play an important role in influenza-induced and allergic airway hyperreactivity. Whereas the transcription factor GATA binding protein 3 (Gata3) is important for the production of IL-5 and -13 by ILC2s in response to IL-33 or -25 stimulation, it is not known whether Gata3 is required for ILC2 development from hematopoietic stem cells. Here, we show that chimeric mice generated with Gata3-deficient fetal liver hematopoietic stem cells fail to develop systemically dispersed ILC2s. In these chimeric mice, in vivo administration of IL-33 or -25 fails to expand ILC2 numbers or to induce characteristic ILC2-dependent IL-5 or -13 production. Moreover, cell-intrinsic Gata3 expression is required for ILC2 development in vitro and in vivo. Using mutant and transgenic mice in which Gata3 gene copy number is altered, we show that ILC2 generation from common lymphoid progenitors, as well as ILC2 homeostasis and cytokine production, is regulated by Gata3 expression levels in a dose-dependent fashion. Collectively, these results identify Gata3 as a critical early regulator of ILC2 development, thereby extending the paradigm of Gata3-dependent control of type 2 immunity to include both innate and adaptive lymphocytes.
authors.affiliation: Immunology Department, Innate Immunity Unit, Institut Pasteur, 75724 Paris, France.
authors.forename: Roel G J
authors.initials: RG
authors.lastname: Klein Wolterink
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serafini
authors.forename: Menno
authors.initials: M
authors.lastname: van Nimwegen
authors.forename: Christian A J
authors.initials: CA
authors.lastname: Vosshenrich
authors.forename: Marjolein J W
authors.initials: MJ
authors.lastname: de Bruijn
authors.forename: Diogo
authors.initials: D
authors.lastname: Fonseca Pereira
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga Fernandes
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000276:immunology; D018628:Gene Dosage / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics* / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000235:genetics* / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; C442281:Mydgf protein, mouse
keywords: asthma; innate immunity