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

• DOI: 10.1016/j.celrep.2023.113425
• Publication Date: 2023-11-10T19:20:08Z
• Authors: Roser Tachó-Piñot; Christopher T. St...; 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
• Keywords: Innate lymphoid cell; BCL6

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