{"doi":"10.1101/2024.09.23.614260","title":"TNFSF13 insufficiency disrupts human colonic epithelial cell-mediated B cell differentiation","abstract":"ABSTRACT Cytokines mediating epithelial and immune cell interactions modulate mucosal healing-a process that goes awry with chronic inflammation as in inflammatory bowel disease. TNFSF13 is a cytokine important for B cell maturation and function, but roles for epithelial TNFSF13 and putative contribution to inflammatory bowel disease are poorly understood. We evaluated functional consequences of a novel monoallelic TNFSF13 variant using biopsies, tissue-derived colonoids and induced pluripotent stem cell (iPSC)-derived colon organoids. TNFSF13 variant colonoids exhibited a >50% reduction in secreted TNFSF13, increased epithelial proliferation, and reduced apoptosis, which was confirmed in iPSC-derived colon organoids. Single cell RNA-sequencing, flow cytometry, and co-immunoprecipitation identified FAS as the predominant colonic epithelial receptor for TNFSF13. Imaging mass cytometry revealed an increase in epithelial-associated B cells in TNFSF13 variant colon tissue sections. Finally, TNFSF13 variant colonoids co-cultured with memory B cells demonstrated a reduction in the production of IgA+ plasma cells compared to control colonoid co-cultures. Our findings support a role for epithelial TNFSF13 as a regulator of colonic epithelial growth and epithelial crosstalk with B cells. SUMMARY Epithelial TNFSF13 regulates colonic epithelial growth and epithelial-B cell interactions. Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491936,"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":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":366501,"name":"Noor Dawany","orcid":"0000-0003-2983-3893","position":1,"is_corresponding":false},{"id":96234,"name":"Ayano Kondo","orcid":"0000-0002-2845-0279","position":2,"is_corresponding":false},{"id":366503,"name":"Kelly Maurer","orcid":"0000-0002-2112-8463","position":3,"is_corresponding":false},{"id":366502,"name":"Tatiana A. Karakasheva","orcid":"0000-0001-9070-2804","position":4,"is_corresponding":false},{"id":366508,"name":"Rawan Shraim","orcid":"0009-0005-5350-3386","position":5,"is_corresponding":false},{"id":913357,"name":"Patrick A. Williams","orcid":"0000-0002-4919-9685","position":6,"is_corresponding":false},{"id":913355,"name":"Louis R. Parham","orcid":"0000-0001-7311-9078","position":7,"is_corresponding":false},{"id":367934,"name":"Lauren Simon","orcid":null,"position":8,"is_corresponding":false},{"id":728394,"name":"Charles Danan","orcid":"0000-0003-2967-9742","position":9,"is_corresponding":false},{"id":287830,"name":"Máire Conrad","orcid":"0000-0003-3561-3029","position":10,"is_corresponding":false},{"id":297082,"name":"David A. Piccoli","orcid":null,"position":11,"is_corresponding":false},{"id":85476,"name":"Marcella Devoto","orcid":"0000-0002-4431-5114","position":12,"is_corresponding":false},{"id":1239055,"name":"Kathleen E Sullivan","orcid":null,"position":13,"is_corresponding":false},{"id":250526,"name":"Klaus H. Kaestner","orcid":"0000-0002-1228-021X","position":14,"is_corresponding":false},{"id":287831,"name":"Judith R. Kelsen","orcid":"0000-0003-0038-318X","position":15,"is_corresponding":false},{"id":444270,"name":"Kathryn E. Hamilton","orcid":"0000-0002-7867-9178","position":16,"is_corresponding":false},{"id":308682,"name":"Xianghui Ma","orcid":"0000-0002-6171-0722","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:08:49.768795Z","pmid":"39386555","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":[]}