Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

Frank Michael Lehmann, Nicole von Burg, Robert Ivanek, Claudia Teufel, Edit Horvath, 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*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

21 Downloads (Pure)

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.

Original languageEnglish
Article number1794
JournalNature Communications
Volume11
Issue number1
Number of pages15
ISSN2041-1723
DOIs
Publication statusPublished - 2020

Fingerprint Dive into the research topics of 'Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation'. Together they form a unique fingerprint.

Cite this