{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:47:55Z","timestamp":1780634875275,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI123730"],"award-info":[{"award-number":["R01 AI123730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK135079"],"award-info":[{"award-number":["R01 DK135079"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA01333"],"award-info":[{"award-number":["P30 CA01333"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 1 diabetes (T1D) is characterized by T\u2010cell responses to islet antigens. Investigations in humans and the nonobese diabetic (NOD) mouse model of T1D have revealed that T\u2010cell reactivity to insulin plays a central role in the autoimmune response. As there is no convenient NOD\u2010based model to study human insulin (hIns) or its T\u2010cell epitopes in the context of spontaneous T1D, we developed a NOD mouse strain transgenically expressing hIns in islets under the control of the human regulatory region. Female NOD.\n                    <jats:italic>hIns<\/jats:italic>\n                    mice developed T1D at approximately the same rate and overall incidence as NOD mice. Islet\u2010infiltrating T cells from NOD.\n                    <jats:italic>hIns<\/jats:italic>\n                    mice recognized hIns peptides; both CD8 and CD4 T\u2010cell epitopes were identified. We also demonstrate that islet\u2010infiltrating T cells from HLA\u2010transgenic NOD.\n                    <jats:italic>hIns<\/jats:italic>\n                    mice can be used to identify potentially patient\u2010relevant hIns T\u2010cell epitopes. Besides serving as an antigen, hIns was expressed in the thymus of NOD.\n                    <jats:italic>hIns<\/jats:italic>\n                    mice and could serve as a protector against T1D under certain circumstances, as previously suggested by genetic studies in humans. NOD.\n                    <jats:italic>hIns<\/jats:italic>\n                    mice and related strains facilitate human\u2010relevant epitope discovery efforts and the investigation of fundamental questions that cannot be readily addressed in humans.\n                  <\/jats:p>","DOI":"10.1002\/eji.202350949","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T01:16:41Z","timestamp":1716427001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Human insulin as both antigen and protector in type 1 diabetes"],"prefix":"10.1002","volume":"54","author":[{"given":"Nitin P.","family":"Amdare","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard D.","family":"Shultz","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory Bar Harbor  Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale L.","family":"Greiner","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, Diabetes Center of Excellence University of Massachusetts Chan Medical School  Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4337-3598","authenticated-orcid":false,"given":"Teresa P.","family":"DiLorenzo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Department of Medicine (Division of Endocrinology and Diabetes) Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Einstein\u2010Mount Sinai Diabetes Research Center Albert Einstein College of Medicine  Bronx New York USA"},{"name":"The Fleischer Institute for Diabetes and Metabolism Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1250"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1120"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061577"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dbi19-0022"},{"key":"e_1_2_10_6_1","first-page":"3390","article-title":"CTLs are targeted to kill \u03b2 cells in patients with type 1 diabetes through recognition of a glucose\u2010regulated preproinsulin epitope","volume":"118","author":"Skowera A.","year":"2008","journal-title":"J. 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