Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3

Roser Tachó-Piñot, Christopher T. Stamper, James I. King, Veronika Matei-Rascu, Erin Richardson, Zhi Li, Luke B. Roberts, John W. Bassett, Felipe Melo-Gonzalez, Rémi Fiancette, I. Hsuan Lin, Alexander Dent, Yohsuke Harada, Conor Finlay, Jenny Mjösberg, David R. Withers, Matthew R. Hepworth

Research output: Contribution to journalArticlepeer-review

Abstract

Innate lymphoid cells (ILCs) are tissue-resident effector cells with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) are classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type 3 effector modules that exhibit significant ontological, transcriptional, phenotypic, and functional heterogeneity. Notably lymphoid tissue inducer (LTi)-like ILC3s mediate effector functions not typically associated with other RORγt-expressing lymphocytes, suggesting that additional transcription factors contribute to dictate ILC3 subset phenotypes. Here, we identify Bcl6 as a subset-defining transcription factor of LTi-like ILC3s in mice and humans. Deletion of Bcl6 results in dysregulation of the LTi-like ILC3 transcriptional program and markedly enhances expression of interleukin-17A (IL-17A) and IL-17F in LTi-like ILC3s in a manner in part dependent upon the commensal microbiota—and associated with worsened inflammation in a model of colitis. Together, these findings redefine our understanding of ILC3 subset biology.

Original languageEnglish
Article number113425
JournalCell Reports
Volume42
Issue number11
DOIs
Publication statusPublished - 28 Nov 2023
Externally publishedYes

Keywords

  • Bcl6
  • CP: Immunology
  • IL-17
  • ILC3
  • innate lymphoid cells
  • intestinal immunity
  • lymphoid tissue inducer
  • microbiota
  • transcription factor

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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