{"doi":"10.1101/2025.09.08.674949","title":"TNF signaling drives expansion of Reg4+ epithelial cells in colitis","abstract":"Abstract Reg4+ secretory cells are upregulated in colitis and promote epithelial repair, but their regulation is poorly understood. We show that TNF-TNFR1 signaling controls Reg4+ cell numbers in mouse and human colonoids and in vivo, with TNFR1 deficiency reducing these cells and TNF restoring them dose-dependently. In UC patients and DSS-colitis, REG4+ cells mark regenerating crypts, and persistent REG4, DUOX2, and TNFR1 expression identifies non-responders to anti-TNF therapy. These findings reveal a TNFR1-dependent mechanism regulating Reg4+ cells and suggest potential strategies to improve therapeutic responses in IBD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559029,"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":0.9472,"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":828102,"name":"Nandini Girish","orcid":null,"position":1,"is_corresponding":false},{"id":564356,"name":"Cambrian Y. Liu","orcid":"0000-0001-6861-6440","position":2,"is_corresponding":false},{"id":338992,"name":"Ying Huang","orcid":"0000-0002-6889-5301","position":3,"is_corresponding":false},{"id":564360,"name":"Tracy C. Grikscheit","orcid":"0000-0003-0842-4820","position":4,"is_corresponding":false},{"id":253838,"name":"D. Brent Polk","orcid":"0000-0001-6680-1554","position":5,"is_corresponding":false},{"id":565264,"name":"Safina Gadeock","orcid":null,"position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","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":[]}