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Aberrant activation of TLRs by self-derived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism by which TLR signaling to self-ligands is regulated remains poorly understood. In this study, we show that \u03b1v integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of \u03b1v from B cells accelerates autoantibody production and autoimmune kidney disease in the Tlr7.1 transgenic mouse model of SLE. Increased autoimmunity was associated with specific expansion of transitional B cells, extrafollicular IgG2c-producing plasma cells, and activation of CD4 and CD8 T cells. Our data show that \u03b1v-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of \u03b1v promotes escape from tolerance. Thus, we identify a new regulatory pathway in autoimmunity and elucidate upstream signals that adjust B cell activation to prevent development of autoimmunity in a mouse model.<\/jats:p>","DOI":"10.4049\/jimmunol.1901056","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T20:51:23Z","timestamp":1598647883000},"page":"1810-1818","source":"Crossref","is-referenced-by-count":19,"title":["B Cell \u03b1v Integrins Regulate TLR-Driven Autoimmunity"],"prefix":"10.1093","volume":"205","author":[{"given":"Mridu","family":"Acharya","sequence":"first","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"},{"name":"Seattle Children\u2019s Research Institute , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-5801","authenticated-orcid":false,"given":"Fiona","family":"Raso","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-0977","authenticated-orcid":false,"given":"Sara","family":"Sagadiev","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"},{"name":"Seattle Children\u2019s Research Institute , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Gilbertson","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-7748","authenticated-orcid":false,"given":"Lauren","family":"Kadavy","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7257-0489","authenticated-orcid":false,"given":"Quan Z","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda M","family":"Stuart","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"},{"name":"Bill and Melinda Gates Foundation , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-5299","authenticated-orcid":false,"given":"Jessica A","family":"Hamerman","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"},{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-0156","authenticated-orcid":false,"given":"Adam","family":"Lacy-Hulbert","sequence":"additional","affiliation":[{"name":"Immunology Program, Benaroya Research Institute at Virginia Mason , Seattle, WA 98101"},{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"2025030417505105000_r1","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1136\/ard.2009.124313","article-title":"Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population","volume":"69","author":"Garc\u00eda-Ortiz","year":"2010","journal-title":"Ann. 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