Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3
- PMID: 37950867
- PMCID: PMC7615641
- DOI: 10.1016/j.celrep.2023.113425
Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3
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.
Keywords: Bcl6; CP: Immunology; IL-17; ILC3; innate lymphoid cells; intestinal immunity; lymphoid tissue inducer; microbiota; transcription factor.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
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