Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

Authors

• H-Y Shih
• G Sciume
• Y Mikami
• L Guo
• HW Sun
• SR Brooks
• JF Urban
• Jr
• FP Davis
• Y Kanno
• JJ O'Shea

Abstract

Innate lymphoid cells (ILCs) play key roles in hostdefense, barrier integrity, and homeostasis andmirror adaptive CD4+ T helper (Th) cell subtypes inboth usage of effector molecules and transcriptionfactors. To better understand the relationship betweenILC subsets and their Th cell counterparts,we measured genome-wide chromatin accessibility.We find that chromatin in proximity to effector genesis selectively accessible in ILCs prior to high-leveltranscription upon activation. Accessibility of theseregions is acquired in a stepwise manner duringdevelopment and changes little after in vitro orin vivo activation. Conversely, dramatic chromatinremodeling occurs in naive CD4+ T cells during Thcell differentiation using a type-2-infection model.This alteration results in a substantial convergenceof Th2 cells toward ILC2 regulomes. Our data indicateextensive sharing of regulatory circuitry acrossthe innate and adaptive compartments of the immunesystem, in spite of their divergent developingpathways.

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