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.
Highlights
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
We show here that natural cytotoxicity receptor (NCR)− ILC3s have a tissue-specific transcriptional signature
Transcripts associated with major histocompatibility complex (MHC) II Ag presentation are relatively enriched in SP NCR− ILC3s
Summary
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. LC3s are primarily tissue-resident cells, which rapidly respond to infections and inflammation by cytokine secretion They express and depend on the transcription factor RAR-related orphan receptor gamma t(RORγt)[1,2] and can be subdivided into natural cytotoxicity receptor (NCR)+ and NCR− cells[3]. T helper (TH)[22] and TH17 cells, ILC3s secrete interleukin (IL)[22] and IL-174–6 and play a role in defense against Citrobacter rodentium infection and in tissue regeneration[7,8,9,10,11] In addition to their function as early cytokine producers, recent analysis has revealed that ILC3 subsets can present antigen (Ag) to CD4+
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