A Gata3 enhancer necessary for ILC2 development and function

The type 2 helper effector program is driven by the master transcription factor GATA3 and can be expressed by subsets of both innate lymphoid cells (ILCs) and adaptive CD4+ T helper (Th) cells. While ILC2s and Th2 cells acquire their type 2 differentiation program under very different contexts, the distinct regulatory mechanisms governing this common program are only partially understood. Here we show that the differentiation of ILC2s, and their concomitant high level of GATA3 expression, are controlled by a Gata3 enhancer, Gata3 +674/762, that plays only a minimal role in Th2 cell differentiation. Mice lacking this enhancer exhibited defects in several but not all type 2 inflammatory responses, depending on the respective degree of ILC2 and Th2 cell involvement. Our study provides molecular insights into the different gene regulatory pathways leading to the acquisition of the GATA3-driven type 2 helper effector program in innate and adaptive lymphocytes. Overall design: ATAC-seq was performed in ILC precursors from bone marrow of Tcf7-mCherry reporter mice Cell population definitions: CLP - Common Lymphoid Precursor Flt3p_aLP - Flt3 positive alpha4beta7 Lymphoid Precursor rEILP - Refined Early Innate Lymphoid Precursor iILCP - Incipient Innate Lymphoid Cell (ILC) Precursor ILCP - ILC Precursor ILC2P - ILC2 Precursor