{"doi":"10.1172/jci162190","title":"Intestinal epithelial HDAC3 and MHC class II coordinate microbiota-specific immunity","abstract":"Aberrant immune responses to resident microbes promote inflammatory bowel disease and other chronic inflammatory conditions. However, how microbiota-specific immunity is controlled in mucosal tissues remains poorly understood. Here, we found that mice lacking epithelial expression of microbiota-sensitive histone deacetylase 3 (HDAC3) exhibited increased accumulation of commensal-specific CD4+ T cells in the intestine, provoking the hypothesis that epithelial HDAC3 may instruct local microbiota-specific immunity. Consistent with this, microbiota-specific CD4+ T cells and epithelial HDAC3 expression were concurrently induced following early-life microbiota colonization. Further, epithelium-intrinsic ablation of HDAC3 decreased commensal-specific Tregs, increased commensal-specific Th17 cells, and promoted T cell-driven colitis. Mechanistically, HDAC3 was essential for NF-κB-dependent regulation of epithelial MHC class II (MHCII). Epithelium-intrinsic MHCII dampened local accumulation of commensal-specific Th17 cells in adult mice and protected against microbiota-triggered inflammation. Remarkably, HDAC3 enabled the microbiota to induce MHCII expression on epithelial cells and limit the number of commensal-specific T cells in the intestine. Collectively, these data reveal a central role for an epithelial histone deacetylase in directing the dynamic balance of tissue-intrinsic CD4+ T cell subsets that recognize commensal microbes and control inflammation.","journal":"Journal of Clinical Investigation","year":2023,"id":319559,"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":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"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":302642,"name":"Tzu‐Yu Shao","orcid":"0000-0002-2896-689X","position":1,"is_corresponding":false},{"id":640690,"name":"Vivienne Woo","orcid":"0000-0001-6152-5167","position":2,"is_corresponding":false},{"id":640693,"name":"Taylor Rice","orcid":"0000-0003-0417-7930","position":3,"is_corresponding":false},{"id":641451,"name":"Laura Engleman","orcid":null,"position":4,"is_corresponding":false},{"id":1029119,"name":"Bailey J. Didriksen","orcid":null,"position":5,"is_corresponding":false},{"id":640692,"name":"Jordan Whitt","orcid":"0000-0002-9968-0143","position":6,"is_corresponding":false},{"id":302643,"name":"David Haslam","orcid":"0000-0002-2143-5869","position":7,"is_corresponding":false},{"id":270438,"name":"Sing Sing Way","orcid":"0000-0001-8948-1952","position":8,"is_corresponding":false},{"id":39745,"name":"Theresa Alenghat","orcid":"0000-0003-4514-3710","position":9,"is_corresponding":false},{"id":640691,"name":"Emily M. Eshleman","orcid":"0000-0003-4828-4105","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T01:07:12.004111Z","pmid":"36602872","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":[]}