{"doi":"10.1101/2022.09.01.505766","title":"IL-10 inhibits STAT1-dependent macrophage accumulation during microbiota-induced colitis","abstract":"Abstract Loss of IL-10R function leads to severe early onset colitis and in murine models is associated with the accumulation of immature inflammatory colonic macrophages. We have shown that IL-10R-deficient colonic macrophages exhibit increased STAT1-dependent gene expression, suggesting that IL-10R-mediated inhibition of STAT1 signaling in newly recruited colonic macrophages might interfere with the development of an inflammatory phenotype. Indeed Stat1 -/- mice exhibit defects in colonic macrophage accumulation following Helicobacter hepaticus infection and IL-10R blockade, and this was phenocopied in mice lacking IFNGR, an inducer of STAT1 activation. Radiation chimeras demonstrated that reduced accumulation of STAT1-deficient macrophages was based on a cell-intrinsic defect. Unexpectedly, mixed radiation chimeras generated with both WT and IL-10R-deficient bone marrow indicated that rather than directly interfering with STAT1 function, IL-10R prevents the generation of a cell extrinsic signal that promotes the accumulation of immature macrophages. These results define essential mechanisms controlling inflammatory macrophage accumulation in inflammatory bowel diseases. Summary Intrinsic STAT1-function drives the accumulation of macrophages within the colon following the loss of IL-10R signaling. IL-10R prevents this STAT1-dependent process through a non-cell autonomous mechanism.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304413,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":749943,"name":"Naresh Singh Redhu","orcid":"0000-0002-0264-9925","position":1,"is_corresponding":false},{"id":5792,"name":"Alal Eran","orcid":"0000-0001-6784-7597","position":2,"is_corresponding":false},{"id":638643,"name":"Bin Bao","orcid":"0000-0001-7610-3426","position":3,"is_corresponding":false},{"id":992677,"name":"Anubhab Nandy","orcid":"0000-0002-2589-398X","position":4,"is_corresponding":false},{"id":449840,"name":"Ying Tang","orcid":"0000-0003-4357-2343","position":5,"is_corresponding":false},{"id":883414,"name":"Shorouk El Sayed","orcid":"0000-0001-9470-2107","position":6,"is_corresponding":false},{"id":297887,"name":"Zeli Shen","orcid":"0000-0002-5278-1625","position":7,"is_corresponding":false},{"id":79204,"name":"Jonathan N. Glickman","orcid":"0000-0003-0910-2655","position":8,"is_corresponding":false},{"id":62839,"name":"James G. Fox","orcid":"0000-0001-9307-6116","position":9,"is_corresponding":false},{"id":5798,"name":"Scott B. Snapper","orcid":"0000-0003-0267-4247","position":10,"is_corresponding":false},{"id":5793,"name":"Bruce Horwitz","orcid":"0000-0002-8123-8728","position":11,"is_corresponding":false},{"id":883415,"name":"Izabel Patik","orcid":"0000-0001-5798-0677","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}