Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

Lehmann, Frank Michael; von Burg, Nicole; Ivanek, Robert; Teufel, Claudia; Horvath, Edit; Peter, Annick; Turchinovich, Gleb; Staehli, Daniel; Eichlisberger, Tobias; Gomez de Agüero, Mercedes; Coto-Llerena, Mairene; Prchal-Murphy, Michaela; Sexl, Veronika; Bentires-Alj, Mohamed; Mueller, Christoph; Finke, Daniela (2020). Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation. Nature communications, 11(1), p. 1794. Nature Publishing Group 10.1038/s41467-020-15612-2

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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.
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