{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:43:39Z","timestamp":1792428219842,"version":"4.5.0"},"reference-count":84,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["22\/0006504"],"award-info":[{"award-number":["22\/0006504"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["G\u20102103\u201005059"],"award-info":[{"award-number":["G\u20102103\u201005059"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type 1 diabetes results from an autoimmune\u2010mediated destruction of pancreatic \u03b2\u2010cells, yet considerable heterogeneity exists regarding disease onset, progression and severity. Emerging evidence suggests that this variability reflects not only differences in immune responses, but also differences in the architecture and immune landscape of the endocrine pancreas. Our recent Steve Morgan Foundation Grand Challenge studies have provided important \u2018lessons from nature\u2019, revealing that the endocrine tissue in the human pancreas exists as a continuum of endocrine objects (EOs), ranging from isolated endocrine cells and small clusters to large islets. These structures differ in their cellular composition, vascularisation, innervation and maturity, creating distinct \u03b2\u2010cell microenvironments that evolve throughout life and may shape susceptibility to autoimmune attack. Strikingly, \u03b2\u2010cells in small EOs are preferentially lost in type 1 diabetes, suggesting EO size and organisation contribute to \u03b2\u2010cell vulnerability. In parallel, we are advancing our understanding of changes in classical and non\u2010classical human leukocyte antigen (HLA\u2010I) expression in type 1 diabetes which can impact \u03b2\u2010cell visibility to autoreactive T cells, and have demonstrated that soluble forms of HLA\u2010I can be released from \u03b2\u2010cells under inflammatory conditions associated with type 1 diabetes. Taken together, our findings support a model in which disease progression is shaped by interactions between a heterogeneous immune response and a heterogeneous endocrine landscape that can vary across the life course. Improving our understanding of how endocrine architecture, immune niches and HLA\u2010mediated antigen presentation interact could identify new opportunities to protect and expand \u03b2\u2010cell populations through targeted therapies in the future.<\/jats:p>","DOI":"10.1111\/dme.70509","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:37:21Z","timestamp":1792427841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New insights into \u03b2\u2010cell vulnerability in type 1 diabetes\u2014Lessons from nature"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3370-6767","authenticated-orcid":false,"given":"Kathryn","family":"Murrall","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Islet Biology Exeter (IBEx), Exeter Centre of Excellence for Diabetes Research (EXCEED) University of Exeter Medical School  Exeter 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(EXCEED) University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9678-7413","authenticated-orcid":false,"given":"Emma","family":"Haxton","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Islet Biology Exeter (IBEx), Exeter Centre of Excellence for Diabetes Research (EXCEED) University of Exeter Medical School  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1144-7767","authenticated-orcid":false,"given":"Christine S.","family":"Flaxman","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, Islet Biology Exeter (IBEx), Exeter Centre of Excellence for Diabetes Research (EXCEED) University of Exeter Medical School  Exeter 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