{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:29:19Z","timestamp":1791178159706,"version":"4.1.0"},"reference-count":61,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,8,4]]},"abstract":"<jats:p>The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)\/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL\/6-lpr\/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL\/6-lpr\/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice.<\/jats:p>","DOI":"10.1084\/jem.20072646","type":"journal-article","created":{"date-parts":[[2008,7,21]],"date-time":"2008-07-21T20:45:44Z","timestamp":1216673144000},"page":"1879-1888","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Tir8\/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens"],"prefix":"10.1084","volume":"205","author":[{"given":"Maciej","family":"Lech","sequence":"first","affiliation":[{"name":"1Medical Policlinic, University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onkar P.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"1Medical Policlinic, University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"1Medical Policlinic, University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emina","family":"Savarese","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Krug","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Garlanda","sequence":"additional","affiliation":[{"name":"3Istituto Clinico Humanitas and Fondazione Humanitas per la Ricerca, I-20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Mantovani","sequence":"additional","affiliation":[{"name":"3Istituto Clinico Humanitas and Fondazione Humanitas per la Ricerca, I-20089 Rozzano, Italy"},{"name":"4University of Milan, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Anders","sequence":"additional","affiliation":[{"name":"1Medical Policlinic, University of Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,7,21]]},"reference":[{"key":"2023072916363491800_BIB1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cell.2007.06.033","volume":"130","year":"2007","journal-title":"Cell."},{"key":"2023072916363491800_BIB2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/83713","volume":"27","year":"2001","journal-title":"Nat. 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