{"doi":"10.1053/j.gastro.2025.06.021","title":"Peyer’s Patch B Cells Sample Transglutaminase-Gluten Complexes and Drive Celiac Disease Autoimmunity","abstract":"BACKGROUND & AIMS: T cells in gut-associated lymphoid tissues (GALT) via the formation of transient enzyme-substrate complexes formed between TG2 and gluten. Where in the body enzymatically active TG2 encounters gluten peptides remains unknown. METHODS: A model to study the celiac disease-relevant T-cell-B-cell interactions in GALT has been developed. Mice expressing HLA-DQ2.5 received TG2-specific B cells and gluten-specific T cells by adoptive transfer and were subsequently orally immunized with a model antigen containing the the B-cell and T-cell epitopes. RESULTS: Orally immunized HLA-DQ2.5 knockin mice developed TG2-specific gut immunoglobulin (Ig)A and serum IgG responses. Activated TG2-specific B cells were present in Peyer's patches and in gut-draining mesenteric lymph nodes, resembling what is seen in human celiac disease. We demonstrate that TG2-specific B cells in Peyer's patches sample TG2 when the protein is perfused into the gut lumen. CONCLUSION: The model supports a mechanism in which TG2-gluten complexes formed in the gut lumen are taken up by TG2-specific B cells in GALT. We propose that this pathway plays an important role in driving the anti-TG2 IgA autoantibody response in patients with celiac disease. The model provides a platform to explore novel approaches for celiac disease therapies.","journal":"Gastroenterology","year":2025,"id":519812,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":1252022,"name":"Liv Kleppa","orcid":"0000-0002-7315-6458","position":1,"is_corresponding":false},{"id":691367,"name":"Alisa E. Dewan","orcid":"0000-0001-7314-5778","position":2,"is_corresponding":false},{"id":1252414,"name":"Maureen Tania Meling","orcid":null,"position":3,"is_corresponding":false},{"id":691364,"name":"Lene S. Høydahl","orcid":"0000-0001-6070-1413","position":4,"is_corresponding":false},{"id":1031835,"name":"Harrison A. Besser","orcid":"0000-0001-9361-7496","position":5,"is_corresponding":false},{"id":430078,"name":"Chaitan Khosla","orcid":"0000-0001-6529-495X","position":6,"is_corresponding":false},{"id":641999,"name":"Ludvig M. Sollid","orcid":"0000-0001-8860-704X","position":7,"is_corresponding":false},{"id":691365,"name":"M. Fleur du Pré","orcid":"0000-0001-9231-643X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"40602545","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":[]}