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To identify disease\u2010relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus\u2010like genomic repeat elements, normally silent, are expressed in patients with systemic autoimmune disease, and whether these retroelements could activate an innate immune response and induce type I IFN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Expression of type I IFN and long interspersed nuclear element 1 (LINE\u20101; L1) was studied by polymerase chain reaction, Western blotting, and immunohistochemistry in samples of kidney tissue from patients with lupus nephritis and minor salivary gland (MSG) tissue from patients with primary Sj\u00f6gren's syndrome (SS). Induction of type I IFN by L1 was investigated by transfection of plasmacytoid dendritic cells (PDCs) or monocytes with an L1\u2010encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Levels of L1 messenger RNA transcripts were increased in lupus nephritis kidneys and in MSG tissue from patients with SS. Transcript expression correlated with the expression of type I IFN and L1 DNA demethylation. L1 open\u2010reading frame 1\/p40 protein and IFN\u03b2 were expressed in MSG ductal epithelial cells and in lupus nephritis kidneys, and IFN\u03b1 was detected in infiltrating PDCs. Transfection of PDCs or monocytes with L1\u2010encoding DNA or RNA induced type I IFN. Inhibition of Toll\u2010like receptor 7 (TLR\u20107)\/TLR\u20108 reduced the induction of IFN\u03b1 by L1 in PDCs, and an inhibitor of IKK\u03b5\/TANK\u2010binding kinase 1 abrogated the induction of type I IFN by L1 RNA in monocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>L1 genomic repeat elements represent endogenous nucleic acid triggers of the type I IFN pathway in SLE and SS and may contribute to initiation or amplification of autoimmune disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.39795","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T06:02:52Z","timestamp":1466748172000},"page":"2686-2696","source":"Crossref","is-referenced-by-count":177,"title":["Expression of Long Interspersed Nuclear Element 1 Retroelements and Induction of Type I Interferon in Patients With Systemic Autoimmune Disease"],"prefix":"10.1002","volume":"68","author":[{"given":"Clio P.","family":"Mavragani","sequence":"first","affiliation":[{"name":"Hospital for Special Surgery, New York, New York, and National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Sagalovskiy","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Guo","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianos","family":"Nezos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathia K.","family":"Kapsogeorgou","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Lu","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liang Zhou","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos A.","family":"Kirou","sequence":"additional","affiliation":[{"name":"Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya V.","family":"Seshan","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haralampos M.","family":"Moutsopoulos","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens Athens 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