{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:59:10Z","timestamp":1790823550515,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease driven by genetic susceptibility and triggered by environmental cues. This review aims to systematically elaborate the full pathogenic cascade of T1DM involving the crosstalk among genetics, environment, immunity and pancreatic target cells, and summarize current preventive and therapeutic strategies together with outstanding unresolved questions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We reviewed published literatures regarding T1DM pathogenesis, preclinical intervention and curative \u03b2 cell replacement therapy, focusing on established immune mechanisms, controversial hypotheses and translational barriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Breakdown of immune tolerance leads to progressive destruction of pancreatic \u03b2 cells mediated by autoreactive CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, resulting in absolute insulin deficiency and lifelong exogenous insulin dependence. Viral infection serves as a major disease trigger, while multiple pathways including \u03b2 cell stress\u2010related neoantigen formation, gut microbiota\u2010intestinal barrier dysfunction, mechanosensing\u2010dependent immune cell homing and epigenetic modification of memory T cells jointly drive disease progression. T1DM follows a 1\u20133 staging framework, providing an intervention window at preclinical stages. Current therapies can merely delay onset, and stem\u2010cell\u2010derived \u03b2 cell transplantation is restricted by allogeneic rejection and recurrent autoimmunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multiple intertwined genetic\u2010environmental\u2010immune events initiate and propagate T1DM. Novel strategies targeting key pathogenic nodes are urgently required to eliminate autoimmune memory, and further translational studies are needed to achieve curative treatment for T1DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71409","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:41:10Z","timestamp":1790822470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Mechanisms and Translational Therapeutic Challenges in Type 1 Diabetes"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-4759","authenticated-orcid":false,"given":"Haijun","family":"Xu","sequence":"first","affiliation":[{"name":"College of Life and Health West Anhui University  Lu'an Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Life and Health West Anhui University  Lu'an Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Jia","sequence":"additional","affiliation":[{"name":"College of Life and Health West Anhui University  Lu'an Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunan","family":"Cuan","sequence":"additional","affiliation":[{"name":"College of Life and Health West Anhui University  Lu'an Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life and Health West Anhui University  Lu'an Anhui Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"8","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1111\/1753-0407.70120","article-title":"A Comprehensive Review of Novel Advances in Type 1 Diabe\u2010 Tes Mellitus","volume":"17","author":"Ebrahimpour Y.","year":"2025","journal-title":"Journal of Diabetes"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40124\u2010025\u201000351\u2010z"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2026.1744422","article-title":"Neoepitopes at the Crossroads of Immunometabolism: Metabolic Remodeling of Antigen Presentation in Type 1 Diabetes","volume":"17","author":"Mittal R.","year":"2026","journal-title":"Frontiers in Immunology"},{"issue":"8","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.2337\/dbi21-0036","article-title":"The \u03b2\u2010Cell in Type 1 Diabetes Pathogenesis: A Victim of Circumstances or an Instigator of Tragic Events?","volume":"71","author":"Mallone R.","year":"2022","journal-title":"Diabetes"},{"issue":"1","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","DOI":"10.4239\/wjd.v16.i1.99496","article-title":"Current Perspectives and the Future of Disease\u2010Modifying Therapies in Type 1 Diabetes","volume":"16","author":"Mondal S.","year":"2025","journal-title":"World Journal of Diabetes"},{"issue":"7","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1902226","article-title":"An Anti\u2010CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes","volume":"381","author":"Herold K. 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