Lehmann, Frank MichaelFrank MichaelLehmannvon Burg, NicoleNicolevon BurgIvanek, RobertRobertIvanekTeufel, ClaudiaClaudiaTeufelHorvath, EditEditHorvathPeter, AnnickAnnickPeterTurchinovich, GlebGlebTurchinovichStaehli, DanielDanielStaehliEichlisberger, TobiasTobiasEichlisbergerGomez de Agüero Tamargo, Maria de la MercedesMaria de la MercedesGomez de Agüero TamargoCoto-Llerena, MaireneMaireneCoto-LlerenaPrchal-Murphy, MichaelaMichaelaPrchal-MurphySexl, VeronikaVeronikaSexlBentires-Alj, MohamedMohamedBentires-AljMüller, ChristophChristophMüller0000-0002-3921-8678Finke, DanielaDanielaFinke2024-09-202024-09-202020-04-14https://boris-portal.unibe.ch/handle/20.500.12422/44956Abstract Although group 3 innate lymphoid cells (ILC3s) are efficient inducers of T cell responses in the spleen, they fail to induce CD4+ T cell proliferation in the gut. The signals regulating ILC3-T cell responses remain unknown. Here, we show that transcripts associated with MHC II antigen presentation are down-modulated in intestinal natural cytotoxicity receptor (NCR)- ILC3s. Further data implicate microbiota-induced IL-23 as a crucial signal for reversible silencing of MHC II in ILC3s, thereby reducing the capacity of ILC3s to present antigen to T cells in the intestinal mucosa. Moreover, IL-23-mediated MHC II suppression is dependent on mTORC1 and STAT3 phosphorylation in NCR- ILC3s. By contrast, splenic interferon-γ induces MHC II expression and CD4+ T cell stimulation by NCR- ILC3s. Our results thus identify biological circuits for tissue-specific regulation of ILC3-dependent T cell responses. These pathways may have implications for inducing or silencing T cell responses in human diseases. Conflict of interest statementen500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.1457963228628510.1038/s41467-020-15612-2