Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA

Walter K. Mowel, Sam J. McCright, Jonathan J. Kotzin, Magalie A. Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P. Spencer, Anthony T. Virtue, En Jun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C. Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku KambayashiIgor E. Brodsky, John J. O'Shea, E. John Wherry, Loyal A. Goff, John L. Rinn, Adam Williams, Richard A. Flavell, Jorge Henao-Mejia

Research output: Contribution to journalArticlepeer-review

Abstract

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Thus, non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs. Mowel et al. find that the locus demarcated by the lncRNA Rroid controls the function and lineage identity of group 1 ILCs by promoting the expression of the transcriptional regulator Id2 in response to IL-15. Their findings demonstrate a critical role for non-coding regulatory elements responsive to unique extracellular cues in the function and homeostasis of individual ILC subsets.

Original languageEnglish (US)
Pages (from-to)435-449.e8
JournalImmunity
Volume47
Issue number3
DOIs
StatePublished - Sep 19 2017

Keywords

  • ILC1
  • Id2
  • innate lymphoid cells
  • lineage identity
  • lncRNA
  • transcriptional regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA'. Together they form a unique fingerprint.

Cite this