Gata3 drives development of ROR gamma t(+) group 3 innate lymphoid cells

N Serafini, Roel Klein Wolterink, N Satoh-Takayama, W Xu, CAJ Vosshenrich, Rudi Hendriks, JP di Santo

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172 Citations (Scopus)

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 ROR gamma t 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 ROR gamma t(+) 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 ROR gamma t(+) 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.
Original languageUndefined/Unknown
Pages (from-to)199-208
Number of pages10
JournalJournal of Experimental Medicine
Volume211
Issue number2
DOIs
Publication statusPublished - 2014

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