{"doi":"10.1038/s41467-025-57744-3","title":"Crohn’s Disease-associated variant in laccase domain containing 1 (LACC1) modulates T cell gene expression, metabolism and T cell function","abstract":"Genome wide association studies (GWAS) identify many risks for Crohn’s disease (CD), including a site near the metabolism gene laccase domain containing 1 (LACC1). We previously found this site near LACC1 was associated with decreased LACC1 expression in T lymphocytes, yet the mechanism affecting gene expression and its links to T cell function and inflammatory disease were unknown. Here we identify variants in the promoter region that influence transcription of LACC1. Direct association of disease-risk variants with lower LACC1 pre-mRNA in human CD4+ T cells is confirmed by comparing transcripts from each allele from donors heterozygous for the LACC1 CD-risk allele. Using gene editing, we validate the function of this promoter region in LACC1 expression in T cells. Human CD4+ T cells with LACC1 gene knockdown show altered metabolism, including reduced oxygen consumption rate, and reduced in vitro regulatory T cell differentiation. Therefore, our study provides a mechanism linking these specific LACC1 variants to colitis by attributing promoter region variants to changes in T cell metabolism and function. Prior studies implicate an allele near laccase domain containing 1 (LACC1) for risk of Crohn’s disease and decreased LACC1 expression in T cells. Using human genome analyzes and mouse genetic models, here the authors link specific LACC1 variants with the modulation of T cell gene expression, metabolism and function.","journal":"Nature Communications","year":2025,"id":520749,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9418,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":809976,"name":"Gabriel Ascui","orcid":"0000-0001-6837-3194","position":1,"is_corresponding":false},{"id":718642,"name":"Martina Dicker","orcid":null,"position":2,"is_corresponding":false},{"id":535206,"name":"Thomas Riffelmacher","orcid":"0000-0002-0372-5272","position":3,"is_corresponding":false},{"id":266581,"name":"Vivek Chandra","orcid":"0000-0002-4047-015X","position":4,"is_corresponding":false},{"id":245044,"name":"Benjamin Joachim Schmiedel","orcid":"0000-0002-9103-9378","position":5,"is_corresponding":false},{"id":700694,"name":"Ting-Fang Chou","orcid":"0000-0001-7095-3518","position":6,"is_corresponding":false},{"id":110385,"name":"Pandurangan Vijayanand","orcid":"0000-0001-7067-9723","position":7,"is_corresponding":false},{"id":266586,"name":"Mitchell Kronenberg","orcid":"0000-0001-6318-6445","position":8,"is_corresponding":false},{"id":809978,"name":"Yingcong Li","orcid":"0000-0002-0746-0531","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40089498","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":[]}