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Proteomic analysis of purified MVs released from islet cells detected the presence of endogenous retrovirus (ERV) antigens, including Env and Gag sequences similar to the well\u2010characterized murine leukemia retroviruses. This raises the possibility that ERV antigens may be expressed in the pancreatic islets via MV secretion. Using virus\u2010like particles produced by co\u2010expressing ERV Env and Gag antigens, and a recombinant gp70 Env protein, we demonstrated that NOD but not diabetes\u2010resistant mice developed anti\u2010Env autoantibodies that increase in titer as disease progresses. A lentiviral\u2010based RNA interference knockdown of Gag revealed that Gag contributes to the MV\u2010induced T\u2010cell response, whose diabetogenic function can be demonstrated via cell\u2010transfer into immune\u2010deficient mice. Finally, we observed that Gag and Env are expressed in NOD islet\u2010derived primary mesenchymal stem cells (MSCs). However, MSCs derived from the islets of diabetes\u2010resistant mice do not express the antigens. Taken together, abnormal ERV activation and secretion of MVs may induce anti\u2010retroviral responses to trigger autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.201646755","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T15:12:48Z","timestamp":1484320368000},"page":"575-584","source":"Crossref","is-referenced-by-count":30,"title":["Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD mice"],"prefix":"10.1002","volume":"47","author":[{"given":"Roman","family":"Bashratyan","sequence":"first","affiliation":[{"name":"Department of Immunology &amp; Microbial Science The Scripps Research Institute  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Regn","sequence":"additional","affiliation":[{"name":"Department of Immunology &amp; Microbial Science The Scripps Research Institute  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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