Abstract
Group 2 innate lymphoid cells (ILC2s) are a subset of ILCs that play a protective role in the response to helminth infection, but they also contribute to allergic lung inflammation. Here, we report that the deletion of the ETS1 transcription factor in lymphoid cells resulted in a loss of ILC2s in the bone marrow and lymph nodes and that ETS1 promotes the fitness of the common progenitor of all ILCs. ETS1-deficient ILC2 progenitors failed to up-regulate messenger RNA for the E protein transcription factor inhibitor ID2, a critical factor for ILCs, and these cells were unable to expand in cytokine-driven in vitro cultures. In vivo, ETS1 was required for the IL-33-induced accumulation of lung ILC2s and for the production of the T helper type 2 cytokines IL-5 and IL-13. IL-25 also failed to elicit an expansion of inflammatory ILC2s when these cells lacked ETS1. Our data reveal ETS1 as a critical regulator of ILC2 expansion and cytokine production and implicate ETS1 in the regulation of Id2 at the inception of ILC2 development.