{"doi":"10.17615/d2rw-pb90","title":"Alterations to chromatin in intestinal macrophages link IL-10 deficiency to inappropriate inflammatory responses","abstract":"Intestinal macrophages are uniquely programmed to tolerate exposure to bacteria without mounting potent inflammatory responses. The cytokine IL-10 maintains the macrophage anti-inflammatory response such that loss of IL-10 results in chronic intestinal inflammation. To investigate how IL-10-deficiency alters intestinal macrophage programming and bacterial tolerance, we studied changes in chromatin accessibility in response to bacteria in macrophages from two distinct niches, the intestine and bone-marrow, from both wild-type and IL-10-deficient mice. In both bone-marrow-derived and intestinal macrophages, we identified chromatin accessibility changes associated with bacterial exposure and IL-10-deficiency. Surprisingly, IL-10-deficient intestinal macrophages adopted chromatin and gene expression patterns characteristic of an inflammatory response, even in the absence of bacteria. Further, if IL-10 protein was added to cells that had previously been IL-10-deficient, it could not revert the chromatin landscape to a normal state. Our results demonstrate that IL-10 deficiency results in stable chromatin alterations in macrophages, even in the absence of bacteria. This supports a model where IL-10-deficiency leads to chromatin alterations that contribute to a loss of intestinal macrophage tolerance to bacteria, which is a primary initiating event in chronic intestinal inflammation.","journal":"UNC Libraries","year":2020,"id":135641,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561987,"name":"Matthew R. Schaner","orcid":"0000-0001-8587-4679","position":1,"is_corresponding":false},{"id":411872,"name":"Mark J. Koruda","orcid":"0000-0001-7098-6862","position":2,"is_corresponding":false},{"id":1090,"name":"Dermot McGovern","orcid":"0000-0001-5621-759X","position":3,"is_corresponding":false},{"id":593760,"name":"Matthew Weiser","orcid":null,"position":4,"is_corresponding":false},{"id":11271,"name":"Karen L. Mohlke","orcid":"0000-0001-6721-153X","position":5,"is_corresponding":false},{"id":542255,"name":"Saangyoung E. Lee","orcid":"0000-0003-3498-184X","position":6,"is_corresponding":false},{"id":525087,"name":"Shehzad Z. Sheikh","orcid":"0000-0002-4238-3674","position":7,"is_corresponding":false},{"id":11678,"name":"Terrence S. Furey","orcid":"0000-0001-5546-9672","position":8,"is_corresponding":false},{"id":11659,"name":"Jeremy M. Simon","orcid":"0000-0003-3906-1663","position":9,"is_corresponding":false},{"id":307850,"name":"Gregory R. Gipson","orcid":"0000-0002-3698-4182","position":10,"is_corresponding":false},{"id":36349,"name":"R. Balfour Sartor","orcid":"0000-0002-7820-632X","position":11,"is_corresponding":false},{"id":593761,"name":"Timothy S. Sadiq","orcid":null,"position":12,"is_corresponding":false},{"id":11673,"name":"Jason D. Lieb","orcid":null,"position":13,"is_corresponding":false},{"id":342419,"name":"James P. Davis","orcid":"0000-0002-8715-7857","position":14,"is_corresponding":false},{"id":593192,"name":"Reza Rahbar","orcid":"0000-0002-6531-5922","position":15,"is_corresponding":false},{"id":233525,"name":"Hans Herfarth","orcid":"0000-0003-4268-823X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:35.237665Z","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":[]}