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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.
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Submitted on : Thursday, September 11, 2014 - 4:02:40 PM
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Nicolas Serafini, Roel G J Klein Wolterink, Naoko Satoh-Takayama, Wei Xu, Christian A. J. Vosshenrich, et al.. Gata3 drives development of RORγt+ group 3 innate lymphoid cells.. Journal of Experimental Medicine, Rockefeller University Press, 2014, 211 (2), pp.199-208. ⟨10.1084/jem.20131038⟩. ⟨pasteur-01063219⟩



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