{"doi":"10.1016/j.celrep.2023.112128","title":"Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells","abstract":"The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD.","journal":"Cell Reports","year":2023,"id":320536,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":512458,"name":"Rachel E. 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Byndloss","orcid":"0000-0002-2122-4156","position":10,"is_corresponding":false},{"id":631455,"name":"Catherine Shelton","orcid":null,"position":11,"is_corresponding":false},{"id":558868,"name":"Janet Markle","orcid":"0000-0003-2189-4368","position":12,"is_corresponding":false},{"id":459909,"name":"Yvonne L. Latour","orcid":"0000-0002-9319-8268","position":13,"is_corresponding":false},{"id":459912,"name":"Margaret M. Allaman","orcid":"0000-0002-2803-1365","position":14,"is_corresponding":false},{"id":422765,"name":"James E. Cassat","orcid":"0000-0002-1199-1167","position":15,"is_corresponding":false},{"id":60566,"name":"Keith T. Wilson","orcid":"0000-0003-4421-1830","position":16,"is_corresponding":false},{"id":500518,"name":"Yash A. Choksi","orcid":"0000-0003-1717-4472","position":17,"is_corresponding":false},{"id":291506,"name":"Christopher S. Williams","orcid":"0000-0002-1541-579X","position":18,"is_corresponding":false},{"id":60556,"name":"Ken S. 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