GSE111871
Runx/Cbfß complexes protect ILC2s from exhaustion during allergic airway inflammation
Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. Therefore, there should be mechanisms to maintain the capacity of ILC2s to produce TH2 cytokines under chronic inflammatory conditions. Here, we report that Runx proteins are essential to prevent exaggerated activation of ILC2, in part by antagonizing GATA-3 function at steady state. However, during allergic inflammation, the absence of Runx in ILC2s impaired their ability to proliferate and produce effector TH2 cytokines and chemokines, but instead induced expression of T cell exhaustion markers including IL-10 and TIGIT. These exhausted ILC2s were unabale to induce type 2 immune responses against repeated allergen inhalation. Thus, Runx proteins protect ILC2s from exhaustion during continuous allergic inflammation. Overall design: RNA-seq data of lung ILC2s from Cbfb +/f PLZF-Cre mice and Cbfb f/f PLZF-Cre mice (biological triplicates). RNA-seq data of cultured lung ILC2s from Cbfb +/f PLZF-Cre mice and Cbfb f/f PLZF-Cre mice (biological triplicates). ChIP-seq data of ILC2s cultured with IL-2/IL-7 or IL-2/IL-7/IL-33 for bindings of CBFb, Runx1, Runx3, GATA-3, and H3K27 acetylation (technical duplicates).