{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:07:04Z","timestamp":1786133224759,"version":"build-2736575974"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    The IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E). In mouse models of crescentic GN (nephrotoxic nephritis) and pristane-induced lupus nephritis, deficiency in IL-17C significantly ameliorated the course of GN in terms of renal tissue injury and kidney function. Deficiency of the unique IL-17C receptor IL-17 receptor E (IL-17RE) provided similar protection against crescentic GN. These protective effects associated with a reduced T\n                    <jats:sub>H<\/jats:sub>\n                    17 response. Bone marrow transplantation experiments revealed that IL-17C is produced by tissue-resident cells, but not by lymphocytes. Finally, IL-17RE was highly expressed by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells, and loss of this expression prevented the T\n                    <jats:sub>H<\/jats:sub>\n                    17 responses and subsequent tissue injury in crescentic GN. Our findings indicate that IL-17C promotes T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell responses and immune-mediated kidney disease\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    IL-17RE expressed on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells. Targeting the IL-17C\/IL-17RE pathway may present an intriguing therapeutic strategy for T\n                    <jats:sub>H<\/jats:sub>\n                    17-induced autoimmune disorders.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017090949","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T10:21:01Z","timestamp":1519640461000},"page":"1210-1222","source":"Crossref","is-referenced-by-count":69,"title":["IL-17C\/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular Inflammation"],"prefix":"10.1681","volume":"29","author":[{"given":"Sonja","family":"Krohn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper F.","family":"Nies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Kapffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Hendrik","family":"Riedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kaffke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anett","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Borchers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver M.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian F.","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Eric","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke R.","family":"Brix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Paust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf A. K.","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Panzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,2,26]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/ni1261","article-title":"A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.","volume":"6","author":"Park","year":"2005","journal-title":"Nat Immunol"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/ni1254","article-title":"Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages.","volume":"6","author":"Harrington","year":"2005","journal-title":"Nat Immunol"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1084\/jem.20071397","article-title":"Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model.","volume":"204","author":"Hirota","year":"2007","journal-title":"J Exp Med"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/ni.1716","article-title":"C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE.","volume":"10","author":"Reboldi","year":"2009","journal-title":"Nat Immunol"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ki.2010.102","article-title":"The Th17 immune response in renal inflammation.","volume":"77","author":"Turner","year":"2010","journal-title":"Kidney Int"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1681\/ASN.2010050536","article-title":"The emergence of TH17 cells as effectors of renal injury.","volume":"22","author":"Kitching","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrneph.2017.112","article-title":"T helper type 17 cells in immune-mediated glomerular disease.","volume":"13","author":"Krebs","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrneph.2017.34","article-title":"T cells and autoimmune kidney disease.","volume":"13","author":"Su\u00e1rez-Fueyo","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1681\/ASN.2008050556","article-title":"The IL-23\/Th17 axis contributes to renal injury in experimental glomerulonephritis.","volume":"20","author":"Paust","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B11-20231016","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1681\/ASN.2015101077","article-title":"IL-17F promotes tissue injury in autoimmune kidney diseases.","volume":"27","author":"Riedel","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1681\/ASN.2013101061","article-title":"CXCL5 drives neutrophil recruitment in TH17-mediated GN.","volume":"26","author":"Disteldorf","year":"2015","journal-title":"J Am Soc 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glomerulonephritis in mice.","volume":"179","author":"Tulone","year":"2011","journal-title":"Am J Pathol"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00467-016-3404-7","article-title":"Innate and adaptive immunity in experimental glomerulonephritis: A pathfinder tale.","volume":"32","author":"Artinger","year":"2017","journal-title":"Pediatr Nephrol"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/ni.2156","article-title":"IL-17C regulates the innate immune function of epithelial cells in an autocrine manner.","volume":"12","author":"Ramirez-Carrozzi","year":"2011","journal-title":"Nat Immunol"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.immuni.2011.09.010","article-title":"Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor 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Immunol"},{"key":"B24-20231016","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ki.2015.296","article-title":"Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus.","volume":"89","author":"Kluger","year":"2016","journal-title":"Kidney Int"},{"key":"B25-20231016","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.clim.2016.04.010","article-title":"T cells and IL-17 in lupus nephritis.","volume":"185","author":"Koga","year":"2017","journal-title":"Clin Immunol"},{"key":"B26-20231016","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1189\/jlb.3A0414-184R","article-title":"An essential role of interleukin-17 receptor signaling in the development of autoimmune glomerulonephritis.","volume":"96","author":"Ramani","year":"2014","journal-title":"J Leukoc Biol"},{"key":"B27-20231016","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000453059","article-title":"Interleukin-17RA promotes humoral responses and 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kidney.","volume":"45","author":"Krebs","year":"2016","journal-title":"Immunity"},{"key":"B40-20231016","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1172\/JCI116710","article-title":"Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.","volume":"92","author":"Wolf","year":"1993","journal-title":"J Clin Invest"},{"key":"B41-20231016","first-page":"95","article-title":"Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells.","volume":"140","author":"Wolf","year":"1992","journal-title":"Am J Pathol"},{"key":"B42-20231016","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ki.2011.108","article-title":"Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis.","volume":"80","author":"Paust","year":"2011","journal-title":"Kidney Int"}],"container-title":["Journal of the American Society of 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