{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:43:05Z","timestamp":1792089785692,"version":"4.4.0"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK099550,DK126456,DK127497,DK097605,DK107541,DK121747,GM109780,AI007051,DK130551,GM008111"],"award-info":[{"award-number":["DK099550,DK126456,DK127497,DK097605,DK107541,DK121747,GM109780,AI007051,DK130551,GM008111"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    Type 1 diabetes (T1D) is an autoimmune disease resulting in pancreatic\n                    <jats:italic>\u03b2<\/jats:italic>\n                    cell destruction. Coxsackievirus B3 (CVB3) infection and melanoma differentiation-associated protein 5\u2013dependent (MDA5-dependent) antiviral responses are linked with T1D development. Mutations within\n                    <jats:italic>IFIH1<\/jats:italic>\n                    , coding for MDA5, are correlated with T1D susceptibility, but how these mutations contribute to T1D remains unclear. Utilizing nonobese diabetic (NOD) mice lacking\n                    <jats:italic>Ifih1<\/jats:italic>\n                    expression (\n                    <jats:italic>KO<\/jats:italic>\n                    ) or containing an in-frame deletion within the ATPase site of the helicase 1 domain of MDA5 (\u0394\n                    <jats:italic>Hel1<\/jats:italic>\n                    ), we tested the hypothesis that partial or complete loss-of-function mutations in MDA5 would delay T1D by impairing proinflammatory pancreatic macrophage and T cell responses. Spontaneous T1D developed in female NOD and\n                    <jats:italic>KO<\/jats:italic>\n                    mice similarly, but was significantly delayed in \u0394\n                    <jats:italic>Hel1<\/jats:italic>\n                    mice, which may be partly due to a concomitant increase in myeloid-derived suppressor cells. Interestingly,\n                    <jats:italic>KO<\/jats:italic>\n                    male mice had increased spontaneous T1D compared with NOD mice. Whereas NOD and\n                    <jats:italic>KO<\/jats:italic>\n                    mice developed CVB3-accelerated T1D, \u0394\n                    <jats:italic>Hel1<\/jats:italic>\n                    mice were protected partly due to decreased type I IFNs, pancreatic infiltrating TNF\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and perforin\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Furthermore, \u0394\n                    <jats:italic>Hel1<\/jats:italic>\n                    MDA5 protein had reduced ATP hydrolysis compared with wild-type MDA5. Our results suggest that dampened MDA5 function delays T1D, yet loss of MDA5 promotes T1D.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.157929","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T12:00:37Z","timestamp":1670932837000},"source":"Crossref","is-referenced-by-count":22,"title":["MDA5-dependent responses contribute to autoimmune diabetes progression and hindrance"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8171-2901","authenticated-orcid":true,"given":"Samuel I.","family":"Blum","sequence":"first","affiliation":[{"name":"Department of Microbiology, Comprehensive Diabetes Center, The University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-530X","authenticated-orcid":true,"given":"Jared P.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of 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