{"doi":"10.1172/jci.insight.186984","title":"Intestinal epithelial Ceacam1 deficiency prevents steroid-refractory acute gut graft-versus-host disease","abstract":"Steroid-refractory gut acute graft-versus-host disease (SR-Gut-aGVHD) is the major cause of nonrelapse death after allogeneic hematopoietic cell transplantation. High numbers of donor-type IL-22+ T cells, IL-22-dependent dysbiosis, and loss of antiinflammatory CX3CR1hi mononuclear phagocytes (MNPs) play critical roles in SR-Gut-aGVHD pathogenesis. CEACAM1 on intestinal epithelial cells (IECs) is proposed to regulate bacterial translocation and subsequent immune responses in the intestine. Here, with imaging mass cytometry (IMC), combined scRNA-Seq with ATAC-Seq, and high-dimensional flow cytometry analysis, we show that CEACAM1 expression was enhanced on IECs in murine and human SR-Gut-aGVHD. Ceacam1 deficiency on host IECs effectively prevented SR-Gut-aGVHD in murine models. Ceacam1 deficiency on IECs resulted in (i) higher numbers of IL-22+IL-10+Foxp3+CD4+ peripheral Tregs (pTregs) and lower numbers of conventional IL-22+CD4+ T (Tcon), Th/Tc1, and Th17 cells in the intestine; (ii) higher prevalence of beneficial commensal bacteria that augment colonic pTreg expansion, with lower prevalence of pathogenic bacteria; and (iii) higher numbers of antiinflammatory CD103-CX3CR1hi MNPs that produce indoleamine 2,3-dioxygenase (IDO) and IL-10, with lower numbers of proinflammatory CD103+CX3CR1lo MNPs that produce IL-6. Thus, specifically targeting IEC CEACAM1 represents a promising approach for prevention of SR-Gut-aGVHD.","journal":"JCI Insight","year":2025,"id":574368,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":1038614,"name":"Moqian Zheng","orcid":null,"position":1,"is_corresponding":false},{"id":1107731,"name":"Qinjian Li","orcid":"0000-0002-6496-8067","position":2,"is_corresponding":false},{"id":108571,"name":"Xiwei Wu","orcid":"0000-0002-7071-1671","position":3,"is_corresponding":false},{"id":1481772,"name":"Boxi Lin","orcid":"0000-0002-9892-7933","position":4,"is_corresponding":false},{"id":279377,"name":"Tae Hyuk Kang","orcid":"0000-0001-9085-8139","position":5,"is_corresponding":false},{"id":108565,"name":"Hanjun Qin","orcid":"0000-0002-0370-0913","position":6,"is_corresponding":false},{"id":325149,"name":"Maciej Kujawski","orcid":"0000-0002-9701-5211","position":7,"is_corresponding":false},{"id":379479,"name":"Raju Pillai","orcid":"0000-0001-8553-4252","position":8,"is_corresponding":false},{"id":1305683,"name":"James Lin","orcid":"0000-0001-7276-3689","position":9,"is_corresponding":false},{"id":284156,"name":"Ryotaro Nakamura","orcid":"0000-0002-9082-0680","position":10,"is_corresponding":false},{"id":289783,"name":"John E. Shively","orcid":"0000-0002-7763-770X","position":11,"is_corresponding":false},{"id":236735,"name":"Paul J. Martin","orcid":"0000-0001-9051-1215","position":12,"is_corresponding":false},{"id":474662,"name":"Defu Zeng","orcid":"0000-0001-9585-1411","position":13,"is_corresponding":false},{"id":474659,"name":"Qingxiao Song","orcid":"0000-0001-9243-5666","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:57:40.686992Z","pmid":"40923321","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":[]}