{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:58:21Z","timestamp":1776959901408,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T00:00:00Z","timestamp":1616803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Welbio-FNRS"},{"name":"Dutch Diabetes Fonds"},{"name":"Indiana Biosciences Research Institute"},{"name":"INNODIA","award":["115797"],"award-info":[{"award-number":["115797"]}]},{"name":"INNODIA HARVEST","award":["945268"],"award-info":[{"award-number":["945268"]}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008871","name":"Juvenile Diabetes Research Foundation United States of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Autoimmun Highlights"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-\u03b1 (IFN\u03b1), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other \u201cdanger signals\u201d. Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To evaluate whether mtdsRNA represents a \u201cdanger signal\u201d for pancreatic beta cells in the context of T1D, we silenced PNPT1 and\/or SUV3 in slowly proliferating human insulin-secreting EndoC-\u03b2H1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Only the simultaneous silencing of PNPT1\/SUV3 induced dsRNA accumulation in EndoC-\u03b2H1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13317-021-00148-2","type":"journal-article","created":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T18:02:38Z","timestamp":1616868158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous mitochondrial double\u2010stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells"],"prefix":"10.1186","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-5078","authenticated-orcid":false,"given":"Alexandra","family":"Coomans de Brach\u00e8ne","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Castela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Any\u00efshai E.","family":"Musuaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorella","family":"Marselli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Decio L.","family":"Eizirik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,27]]},"reference":[{"issue":"5","key":"148_CR1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrendo.2016.30","volume":"12","author":"A Op de Beeck","year":"2016","unstructured":"Op de Beeck A, Eizirik DL. 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Hepatol Baltim Md ao\u00fbt. 2020;72(2):609\u201325.","journal-title":"Hepatol Baltim Md ao\u00fbt"}],"container-title":["Autoimmunity Highlights"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13317-021-00148-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13317-021-00148-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13317-021-00148-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,27]],"date-time":"2021-03-27T18:02:57Z","timestamp":1616868177000},"score":1,"resource":{"primary":{"URL":"https:\/\/autoimmunhighlights.biomedcentral.com\/articles\/10.1186\/s13317-021-00148-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,27]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["148"],"URL":"https:\/\/doi.org\/10.1186\/s13317-021-00148-2","relation":{},"ISSN":["2038-0305","2038-3274"],"issn-type":[{"value":"2038-0305","type":"print"},{"value":"2038-3274","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,27]]},"assertion":[{"value":"28 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The use of human islets was approved by the local ethics committee of Pisa, Italy.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}