{"doi":"10.7554/elife.100535.2.sa2","title":"Reviewer #2 (Public review): The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes","abstract":"In autoimmune Type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans — islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8+T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA+ T cells — a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.","journal":null,"year":2025,"id":562751,"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":0.9437,"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":1465567,"name":"Christian M Schürch","orcid":null,"position":1,"is_corresponding":false},{"id":1465568,"name":"Salil S Bhate","orcid":null,"position":2,"is_corresponding":false},{"id":1465569,"name":"Darci J Phillips","orcid":null,"position":3,"is_corresponding":false},{"id":235280,"name":"Arabella Young","orcid":"0000-0002-6845-9753","position":4,"is_corresponding":false},{"id":109712,"name":"Shen Dong","orcid":"0000-0001-8839-7046","position":5,"is_corresponding":false},{"id":1328270,"name":"Hunter A Martinez","orcid":null,"position":6,"is_corresponding":false},{"id":381353,"name":"Gernot Kaber","orcid":"0000-0002-6184-5192","position":7,"is_corresponding":false},{"id":381352,"name":"Nadine Nagy","orcid":"0000-0002-2638-2436","position":8,"is_corresponding":false},{"id":1165858,"name":"Sasvath Ramachandran","orcid":null,"position":9,"is_corresponding":false},{"id":1328271,"name":"Janet Meng","orcid":null,"position":10,"is_corresponding":false},{"id":1465570,"name":"Eva Korpos","orcid":null,"position":11,"is_corresponding":false},{"id":1465571,"name":"Jeffrey A Bluestone","orcid":null,"position":12,"is_corresponding":false},{"id":1465572,"name":"Garry P Nolan","orcid":null,"position":13,"is_corresponding":false},{"id":1465573,"name":"Paul L Bollyky","orcid":null,"position":14,"is_corresponding":false},{"id":1465566,"name":"Graham L Barlow","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:09.638214Z","pmid":null,"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":[]}