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Podocytes are an integral component of the kidney filtration barrier and podocyte injury leads to proteinuria. Here we show that podocytes, which receive signals from the vascular space including circulating antigens, constitutively express <jats:styled-content style=\"fixed-case\">TLR1<\/jats:styled-content>\u20136 and <jats:styled-content style=\"fixed-case\">TLR8<\/jats:styled-content>. We find that podocytes can respond to <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> ligands including staphylococcal enterotoxin B (<jats:styled-content style=\"fixed-case\">SEB<\/jats:styled-content>), poly I:C, or lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) with pro\u2010inflammatory cytokine release and activation of type I interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>) signalling. This in turn stimulates podocyte <jats:styled-content style=\"fixed-case\">B7<\/jats:styled-content>\u20101 expression and actin remodelling <jats:italic>in vitro<\/jats:italic> and transient proteinuria <jats:italic>in vivo<\/jats:italic>. Importantly, the treatment of mice with a type I <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> receptor\u2010blocking antibody (Ab) prevents <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced proteinuria. These results significantly extend our understanding of podocyte response to immune stimuli and reveal a novel mechanism for infection\u2010 or inflammation\u2010induced transient proteinuria. Dysregulation or aberrant activation of this response may result in persistent proteinuria and progressive glomerular disease. In summary, the inhibition of glomerular type I <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> signalling with anti\u2010<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> Abs may be a novel therapy for proteinuric kidney diseases. Copyright \u00a9 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4235","type":"journal-article","created":{"date-parts":[[2013,7,8]],"date-time":"2013-07-08T14:17:21Z","timestamp":1373293041000},"page":"248-256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Inhibition of type I interferon signalling prevents <scp>TLR<\/scp> ligand\u2010mediated proteinuria"],"prefix":"10.1002","volume":"231","author":[{"given":"Sevgi","family":"Gurkan","sequence":"first","affiliation":[{"name":"Child Health Institute of New Jersey, Department of Pediatrics Rutgers, The State University of New Jersey New Brunswick NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Cabinian","sequence":"additional","affiliation":[{"name":"Child Health Institute of New Jersey, Department of Pediatrics Rutgers, The State University of New Jersey New Brunswick NJ 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