{"doi":"10.1016/j.mucimm.2025.02.005","title":"Interleukin-10 production by innate lymphoid cells restricts intestinal inflammation in mice","abstract":"Interleukin-10 (IL-10) is an immunomodulatory cytokine critical for intestinal immune homeostasis. IL-10 is produced by various immune cells but IL-10 receptor signaling in intestinal CX 3 CR1 + mononuclear phagocytes is necessary to prevent spontaneous colitis in mice. Here, we utilized fluorescent protein reporters and cell-specific targeting and found that Rorc -expressing innate lymphoid cells (ILCs) produce IL-10 in response to anti-CD40-mediated intestinal inflammation. Deletion of Il10 specifically in Rorc -expressing ILCs led to phenotypic changes in intestinal macrophages and exacerbated both innate and adaptive immune-mediated models of experimental colitis. The population of IL-10 + producing ILCs shared markers with both ILC2 and ILC3 with nearly all ILC3s being of the NCR + subtype. Interestingly, Ccl26 was enriched in IL-10 + ILCs and was markedly reduced in IL-10-deficient ILC3s. Since CCL26 is a ligand for CX 3 CR1, we employed RNA in situ hybridization and observed increased numbers of ILCs in close proximity to Cx3cr1 -expressing cells under inflammatory conditions. Finally, we generated transgenic Rorc tdTomato reporter mice that faithfully marked RORγt + cells that could rescue disease pathology and aberrant macrophage phenotype following adoptive transfer into mice with selective Il10 deficiency in ILC3s. These results demonstrate that IL-10 production by a population of ILCs functions to promote immune homeostasis in the intestine possibly via direct effects on intestinal macrophages.","journal":"Mucosal Immunology","year":2025,"id":517942,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":818980,"name":"Justin Jacobse","orcid":"0000-0002-1899-0319","position":1,"is_corresponding":false},{"id":291498,"name":"Jennifer M. 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Hawkins","orcid":null,"position":11,"is_corresponding":false},{"id":1159911,"name":"Andrew P Pahnke","orcid":"0009-0000-2761-369X","position":12,"is_corresponding":false},{"id":1385394,"name":"M. Khalil","orcid":null,"position":13,"is_corresponding":false},{"id":86848,"name":"M. Kay Washington","orcid":"0000-0002-9589-7695","position":14,"is_corresponding":false},{"id":60566,"name":"Keith T. Wilson","orcid":"0000-0003-4421-1830","position":15,"is_corresponding":false},{"id":291506,"name":"Christopher S. Williams","orcid":"0000-0002-1541-579X","position":16,"is_corresponding":false},{"id":290007,"name":"R. Stokes Peebles","orcid":"0000-0002-1429-7875","position":17,"is_corresponding":false},{"id":231799,"name":"Liza Konnikova","orcid":"0000-0003-4804-5497","position":18,"is_corresponding":false},{"id":500518,"name":"Yash A. 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