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.

Scientific Focus Area: Institute, Center, and Scientific Directors

This page was last updated on Friday, March 26, 2021