{"doi":"10.3389/fimmu.2022.856966","title":"BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis","abstract":"Introduction In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodomain and extra-terminal domain (BET) proteins alters usage of DNA regulatory elements responsible for driving inflammatory gene expression. We determined if the BET inhibitor, (+)-JQ1, could suppress inflammatory activation of macrophages in Il10 -/- mice. Methods We performed ATAC-seq and RNA-seq on Il10 -/- bone marrow-derived macrophages (BMDMs) cultured in the presence and absence of lipopolysaccharide (LPS) with and without treatment with (+)-JQ1 and evaluated changes in chromatin accessibility and gene expression. Germ-free Il10 -/- mice were treated with (+)-JQ1, colonized with fecal slurries and underwent histological and molecular evaluation 14-days post colonization. Results Treatment with (+)-JQ1 suppressed LPS-induced changes in chromatin at distal regulatory elements associated with inflammatory genes, particularly in regions that contain motifs for AP-1 and IRF transcription factors. This resulted in attenuation of inflammatory gene expression. Treatment with (+)-JQ1 in vivo resulted in a mild reduction in colitis severity as compared with vehicle-treated mice. Conclusion We identified the mechanism of action associated with a new class of compounds that may mitigate aberrant macrophage responses to bacteria in colitis.","journal":"Frontiers in Immunology","year":2022,"id":272668,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"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":814644,"name":"Ana Berglind","orcid":"0000-0002-8462-7104","position":1,"is_corresponding":false},{"id":561985,"name":"Meaghan M. Kennedy Ng","orcid":"0000-0003-4612-7560","position":2,"is_corresponding":false},{"id":561986,"name":"Benjamin P. Keith","orcid":"0000-0003-1398-5569","position":3,"is_corresponding":false},{"id":814959,"name":"Zachary J. Lynch","orcid":null,"position":4,"is_corresponding":false},{"id":561987,"name":"Matthew R. Schaner","orcid":"0000-0001-8587-4679","position":5,"is_corresponding":false},{"id":525088,"name":"Erin C. Steinbach","orcid":"0000-0002-6165-8928","position":6,"is_corresponding":false},{"id":279301,"name":"Jeremy Herzog","orcid":"0009-0002-2285-2549","position":7,"is_corresponding":false},{"id":814645,"name":"Omar K. Trad","orcid":"0000-0003-1002-5642","position":8,"is_corresponding":false},{"id":267798,"name":"William R. Jeck","orcid":"0000-0003-0257-4529","position":9,"is_corresponding":false},{"id":270825,"name":"Janelle C. Arthur","orcid":"0000-0002-4796-0207","position":10,"is_corresponding":false},{"id":11659,"name":"Jeremy M. Simon","orcid":"0000-0003-3906-1663","position":11,"is_corresponding":false},{"id":36349,"name":"R. Balfour Sartor","orcid":"0000-0002-7820-632X","position":12,"is_corresponding":false},{"id":11678,"name":"Terrence S. Furey","orcid":"0000-0001-5546-9672","position":13,"is_corresponding":false},{"id":525087,"name":"Shehzad Z. Sheikh","orcid":"0000-0002-4238-3674","position":14,"is_corresponding":false},{"id":814643,"name":"Michelle Hoffner O’Connor","orcid":"0000-0002-2154-7406","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:27:47.926496Z","pmid":"35401533","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":[]}