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Significance Group 2 innate lymphoid cells (ILC2s) and adaptive CD4+ T helper type 2 (Th2) cells express a common effector program orchestrated by the “master” transcription factor GATA3 that is acquired through development or differentiation, respectively. To elucidate the regulatory mechanisms controlling the acquisition of this shared program, we used a combination of chromatin accessibility data and CRISPR/Cas9-mediated deletion, which revealed aGata3 enhancer necessary for ILC2 development and function. Notably, this enhancer was largely dispensable for Th2 cell differentiation. Thus, ILC2s and Th2 cells display different requirements for the induction of a common type 2 helper effector program.

A Gata3 enhancer necessary for ILC2 development and function