| First Author | Riedel JH | Year | 2016 |
| Journal | J Am Soc Nephrol | Volume | 27 |
| Issue | 12 | Pages | 3666-3677 |
| PubMed ID | 27030744 | Mgi Jnum | J:293085 |
| Mgi Id | MGI:6435854 | Doi | 10.1681/ASN.2015101077 |
| Citation | Riedel JH, et al. (2016) IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases. J Am Soc Nephrol 27(12):3666-3677 |
| abstractText | The TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4(+) T cells and gammadelta T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene-deficient mice, IL-17F-neutralizing antibodies, and adoptive transfer experiments into Rag1(-/-) mice demonstrated that CD4(+) T cell-derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F-deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F-deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F-deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti-IL-17 cytokine therapies in TH17-mediated human autoimmune diseases. |
