{"doi":"10.1016/j.mucimm.2025.07.005","title":"Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling","abstract":"Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide continuous surveillance of the intestinal epithelium. We report that mice harboring a microbiota-specific hyperproliferative γδ IEL (γδ HYP ) phenotype also upregulate the expression of the ectonucleotidase CD39, a marker of regulatory γδ T cells. Enhanced TCR and IL-15 signaling correlates with a progression from a naïve-like CD39 neg γδ IEL to a more mature, tissue-adapted CD39 hi IEL population. We found that TCRγδ activation drives CD122-mediated CD39 upregulation on γδ HYP IELs and increased mucosal IL-15 further amplifies CD39 expression in these cells. Further investigation revealed that CD39 induction requires sustained exposure to the γδ HYP -associated microbiota. Moreover, CD39 hi γδ IELs exhibit a reduced capacity to produce pro-inflammatory cytokine, which may explain the lack of histopathology in γδ HYP mice. Overall, our study identifies a previously unappreciated mechanism by which an altered microbiota amplifies CD39 expression on γδ HYP IELs, leading to the expansion of γδ IELs with regulatory potential.","journal":"Mucosal Immunology","year":2025,"id":553590,"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":0.9526,"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":1162395,"name":"Harsimran Kaur","orcid":"0000-0003-2667-1091","position":1,"is_corresponding":false},{"id":1001733,"name":"Jia Luo","orcid":"0009-0001-1224-4294","position":2,"is_corresponding":false},{"id":1099789,"name":"Mai-Uyen Nguyen","orcid":"0000-0003-0936-2019","position":3,"is_corresponding":false},{"id":1002010,"name":"Alyssa Laguerta","orcid":null,"position":4,"is_corresponding":false},{"id":37821,"name":"Andrew Fong","orcid":"0000-0003-3436-7751","position":5,"is_corresponding":false},{"id":1246558,"name":"Neema Skariah","orcid":null,"position":6,"is_corresponding":false},{"id":85081,"name":"Rafael J. Argüello","orcid":"0000-0001-9785-3883","position":7,"is_corresponding":false},{"id":241177,"name":"Michael P. Verzi","orcid":"0000-0003-4082-4330","position":8,"is_corresponding":false},{"id":1245936,"name":"Mahima Swamy","orcid":"0000-0003-3977-3425","position":9,"is_corresponding":false},{"id":60556,"name":"Ken S. Lau","orcid":"0000-0001-8438-0319","position":10,"is_corresponding":false},{"id":665230,"name":"Karen L. Edelblum","orcid":"0000-0001-8288-4898","position":11,"is_corresponding":false},{"id":724578,"name":"Sara Alonso","orcid":"0000-0003-0560-6362","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:54:41.819682Z","pmid":"40683453","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":[]}