| First Author | Dey I | Year | 2024 |
| Journal | J Immunol | Volume | 213 |
| Issue | 6 | Pages | 767-778 |
| PubMed ID | 39082925 | Mgi Jnum | J:359656 |
| Mgi Id | MGI:7751059 | Doi | 10.4049/jimmunol.2400124 |
| Citation | Dey I, et al. (2024) C/EBPdelta Mediates Immunity to Renal Autoinflammatory Disorders in a Stage-specific Manner. J Immunol 213(6):767-778 |
| abstractText | Kidney disease represents a major medical and economic burden for which improved treatments are urgently needed. 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) delta is elevated in kidney biopsies from multiple manifestations of human AGN. C/EBPdelta is similarly upregulated in a mouse model of anti-glomerular basement membrane protein-mediated kidney disease, and Cebpd-/- mice were fully refractory to disease. Although C/EBPdelta is expressed in a variety of cell types, C/EBPdelta was required only in the radioresistant compartment to drive GN pathology. C/EBPdelta induced expression of several IL-17-induced 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-C/EBPdelta pathway to renal fibrotic events. Surprisingly, deficiency of either C/EBPdelta or the IL-17 receptor caused kidney fibrosis to be enhanced. Thus, C/EBPdelta and IL-17 play divergent and apparently stage-specific roles in the pathogenesis of kidney disease. |
