Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation
F. Lehmann, Nicole von Burg, Robert Ivánek, Claudia Teufel, Edit Horváth, Annick Peter, Gleb Turchinovich, Daniel Staehli, Tobias Eichlisberger, Mercedes Gomez de Agüero, Mairene Coto‐Llerena, Michaela Prchal‐Murphy, Veronika Sexl, Mohamed Bentires‐Alj, Christoph Mueller, Daniela Finke
Abstract
Abstract 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.