{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:42:38Z","timestamp":1793392958584,"version":"4.5.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI150297"],"award-info":[{"award-number":["R01AI150297"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01CA248919"],"award-info":[{"award-number":["R01CA248919"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,3,28]]},"abstract":"<jats:p>\n                    The events that initiate autoimmune diabetes in nonobese diabetic (NOD) mice remain poorly understood. CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are both required to develop disease, but their relative roles in initiating disease are unclear. To test whether CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration into islets requires damage to \u03b2 cells induced by autoreactive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, we inactivated\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    in nonobese diabetic (NOD) mice (NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212-<\/jats:sup>\n                    ) using CRISPR\/Cas9 targeting to eliminate cross-presentation by type 1 conventional dendritic cells (cDC1s). Similar to C57BL\/6\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, cDC1 in NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice are unable to cross-present cell-associated antigens to prime CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, while cDC1 from heterozygous NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice cross-present normally. Further, NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice fail to develop diabetes while heterozygous NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice develop diabetes similarly to wild-type NOD mice. NOD.\n                    <jats:italic>Wdfy4<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice remain capable of processing and presenting\u00a0major histocompatibility complex class II (MHC-II)-restricted autoantigens and can activate \u03b2 cell-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in lymph nodes. However, disease in these mice does not progress beyond peri-islet inflammation. These results indicate that the priming of autoreactive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in NOD mice requires cross-presentation by cDC1. Further, autoreactive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells appear to be required not only to develop diabetes, but to recruit autoreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells into islets of NOD mice, perhaps in response to progressive \u03b2 cell damage.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2219956120","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T15:10:16Z","timestamp":1679325016000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["WDFY4 deficiency in NOD mice ameliorates autoimmune diabetes and insulitis"],"prefix":"10.1073","volume":"120","author":[{"given":"Stephen T.","family":"Ferris","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-9938","authenticated-orcid":false,"given":"Tiantian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray A.","family":"Ohara","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiya","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunkyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa L.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1538\/expanim1978.29.1_1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.381"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/329599a0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25350"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.313940"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.166.4.823"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231244"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06406"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.606434"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804154"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03860.x"},{"key":"e_1_3_4_12_2","first-page":"3390","article-title":"CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope","volume":"118","author":"Skowera A.","year":"2008","unstructured":"A. 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