Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and transcription factors. To better understand ILC subsets and their relationship with Th cells, we measured genome-wide chromatin accessibility. We found that chromatin in proximity to effector genes was selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions was acquired in a stepwise manner during development and changed little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurred in naïve CD4+ T cells during Th cell differentiation using a type 2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways. Integrated analysis of epigenome and transcriptome data from innate lymphoid cells and their progenitors