IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases
| Autor: | Ulf Panzer, Christian Krebs, Hans-Joachim Paust, Oliver M. Steinmetz, Malte A. Kluger, Rolf A.K. Stahl, Sonja Krohn, Jan-Eric Turner, Jan-Hendrik Riedel |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Adoptive cell transfer Neutrophils medicine.medical_treatment Autoimmune Diseases Mice 03 medical and health sciences Glomerulonephritis 0302 clinical medicine Immune system medicine Animals Kidney business.industry Interleukin-17 General Medicine medicine.disease CXCL1 Basic Research 030104 developmental biology Cytokine medicine.anatomical_structure Nephrology Immunology Interleukin 17 business Nephritis 030215 immunology |
| Zdroj: | Journal of the American Society of Nephrology. 27:3666-3677 |
| ISSN: | 1533-3450 1046-6673 |
| DOI: | 10.1681/asn.2015101077 |
| Popis: | 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 γδ 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. |
| Databáze: | OpenAIRE |
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