Tachó-Piñot, RoserStamper, Christopher T.King, James I.Matei-Rascu, VeronikaRichardson, ErinLi, ZhiRoberts, Luke B.Bassett, John W.Melo-Gonzalez, FelipeFiancette, RémiLin, I-HsuanDent, AlexanderHarada, YohsukeFinlay, ConorMjösberg, JennyWithers, David R.Hepworth, Matthew R.2024-06-132024-06-132023Tachó-Piñot R, Stamper CT, King JI, et al. Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3. Cell Rep. 2023;42(11):113425. doi:10.1016/j.celrep.2023.113425https://hdl.handle.net/1805/41526Innate 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.en-USPublisher PolicyBcl6ImmunologyIL-17ILC3Innate lymphoid cellsIntestinal immunityLymphoid tissue inducerMicrobiotaTranscription factorArticle