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Emerging data have implicated Th17 cells and IL-17 signaling in the underlying pathogenesis of autoantibody-induced glomerulonephritis (AGN). However, the downstream transduction pathways mediated by IL-17 in autoimmunity are not well defined. In this article, we show that CCAAT\/enhancer-binding protein (C\/EBP) \u03b4 is elevated in kidney biopsies from multiple manifestations of human AGN. C\/EBP\u03b4 is similarly upregulated in a mouse model of anti-glomerular basement membrane protein\u2013mediated kidney disease, and Cebpd\u2212\/\u2212 mice were fully refractory to disease. Although C\/EBP\u03b4 is expressed in a variety of cell types, C\/EBP\u03b4 was required only in the radioresistant compartment to drive GN pathology. C\/EBP\u03b4 induced expression of several IL-17\u2013induced kidney injury markers and cytokines implicated in disease, including Il6 and Lcn2. Because mouse AGN models do not progress to fibrosis, we employed a nephrotoxic injury model using aristolochic acid I to assess the contribution of the IL-17\u2013C\/EBP\u03b4 pathway to renal fibrotic events. Surprisingly, deficiency of either C\/EBP\u03b4 or the IL-17 receptor caused kidney fibrosis to be enhanced. Thus, C\/EBP\u03b4 and IL-17 play divergent and apparently stage-specific roles in the pathogenesis of kidney disease.<\/jats:p>","DOI":"10.4049\/jimmunol.2400124","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T13:57:31Z","timestamp":1722434251000},"page":"767-778","source":"Crossref","is-referenced-by-count":5,"title":["C\/EBP\u03b4 Mediates Immunity to Renal Autoinflammatory Disorders in a Stage-specific Manner"],"prefix":"10.1093","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0538-124X","authenticated-orcid":false,"given":"Ipsita","family":"Dey","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-4004","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-3728","authenticated-orcid":false,"given":"Tiffany C","family":"Taylor","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-5686","authenticated-orcid":false,"given":"Doureradjou","family":"Peroumal","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariaki","family":"Asada","sequence":"additional","affiliation":[{"name":"III Department of Medicine, University Medical Center Hamburg\u2013Eppendorf , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Panzer","sequence":"additional","affiliation":[{"name":"III Department of Medicine, University Medical Center Hamburg\u2013Eppendorf , Hamburg ,","place":["Germany"]},{"name":"Hamburg Center for Translational Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha S","family":"Biswas","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-8766","authenticated-orcid":false,"given":"Esta","family":"Sterneck","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute , Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":false,"given":"Sarah L","family":"Gaffen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Division of Rheumatology and Clinical Immunology , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"2025012305153313400_r1","doi-asserted-by":"crossref","first-page":"103326","DOI":"10.1016\/j.autrev.2023.103326","article-title":"Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019","volume":"22","author":"Cao","year":"2023","journal-title":"Autoimmun. 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