{"doi":"10.1126/sciimmunol.adf4312","title":"Gluten induces rapid reprogramming of natural memory αβ and γδ intraepithelial T cells to induce cytotoxicity in celiac disease","abstract":"Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4 + T cell activation culminates in intraepithelial T cell (T-IEL)–mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4 + follicular T helper (T FH ) cells, regulatory T cells (T regs ), and natural CD8 + αβ and γδ T-IELs. Natural CD8 + αβ and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4 + T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4 + T cells after gluten ingestion.","journal":"Science Immunology","year":2023,"id":321234,"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":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":858673,"name":"Theo Botella","orcid":"0000-0003-0331-2491","position":1,"is_corresponding":false},{"id":1033204,"name":"Christine S. Moon","orcid":"0000-0001-8717-2435","position":2,"is_corresponding":false},{"id":1033205,"name":"Samhita Rao","orcid":"0000-0003-4155-7158","position":3,"is_corresponding":false},{"id":1033206,"name":"Jared Gelbs","orcid":"0009-0004-8575-3155","position":4,"is_corresponding":false},{"id":537938,"name":"Liang Cheng","orcid":"0000-0001-6049-5293","position":5,"is_corresponding":false},{"id":849843,"name":"Jonathan Miller","orcid":"0000-0002-8189-5453","position":6,"is_corresponding":false},{"id":859592,"name":"Alyssa M. Bacarella","orcid":null,"position":7,"is_corresponding":false},{"id":885713,"name":"Javier A. Garcia‐Vilas","orcid":"0000-0003-0700-5069","position":8,"is_corresponding":false},{"id":1033207,"name":"Justin Vargas","orcid":"0009-0009-5123-9904","position":9,"is_corresponding":false},{"id":493581,"name":"Xuechen Yu","orcid":"0000-0001-5659-1418","position":10,"is_corresponding":false},{"id":553713,"name":"Izabela Krupska","orcid":"0009-0008-8111-6780","position":11,"is_corresponding":false},{"id":225057,"name":"Erin Bush","orcid":"0000-0001-7038-2321","position":12,"is_corresponding":false},{"id":1033208,"name":"Reuben Garcia-Carrasquillo","orcid":"0000-0002-8970-8544","position":13,"is_corresponding":false},{"id":218572,"name":"Benjamin Lebwohl","orcid":"0000-0001-9422-4774","position":14,"is_corresponding":false},{"id":484600,"name":"Suneeta Krishnareddy","orcid":"0000-0001-6054-4593","position":15,"is_corresponding":false},{"id":281004,"name":"Suzanne K. Lewis","orcid":"0000-0002-6651-4499","position":16,"is_corresponding":false},{"id":420696,"name":"Peter H.R. Green","orcid":"0000-0001-6839-9634","position":17,"is_corresponding":false},{"id":270227,"name":"Govind Bhagat","orcid":"0000-0001-6250-048X","position":18,"is_corresponding":false},{"id":344435,"name":"Kelley S. Yan","orcid":"0000-0001-9826-7261","position":19,"is_corresponding":false},{"id":605681,"name":"Arnold Han","orcid":"0000-0002-2667-5335","position":20,"is_corresponding":false},{"id":615136,"name":"Adam Kornberg","orcid":"0000-0002-8099-9699","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37450575","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":[]}