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.

doi.org/10.1084/jem.20131038, hdl.handle.net/1765/69786
The Journal of Experimental Medicine
Department of Pulmonology

Serafini, N, Klein Wolterink, R.G.J, Satoh-Takayama, N, Xu, W, Vosshenrich, C.A, Hendriks, R.W, & di Santo, J.P. (2014). Gata3 drives development of RORγt+ group 3 innate lymphoid cells. The Journal of Experimental Medicine, 211(2), 199–208. doi:10.1084/jem.20131038