{"doi":"10.1084/jem.20241993","title":"Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency","abstract":"Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.","journal":"The Journal of Experimental Medicine","year":2025,"id":525652,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9658,"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":281846,"name":"Francesca Pala","orcid":"0000-0003-4537-9061","position":1,"is_corresponding":false},{"id":264081,"name":"Poorani Subramanian","orcid":"0000-0003-4371-7290","position":2,"is_corresponding":false},{"id":383897,"name":"Cihan Oguz","orcid":"0000-0002-2860-3546","position":3,"is_corresponding":false},{"id":108651,"name":"Benjamin Schwarz","orcid":"0000-0002-5894-953X","position":4,"is_corresponding":false},{"id":621284,"name":"Ai Ing Lim","orcid":"0000-0001-8834-3136","position":5,"is_corresponding":false},{"id":338357,"name":"Andrew S. 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