Journal
KIDNEY INTERNATIONAL
Volume 95, Issue 6, Pages 1418-1432Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2018.12.031
Keywords
BTBR ob/ob; diabetic nephropathy; IL-17A; inflammation
Categories
Funding
- Fondecyt [1160465]
- Division of Nephrology, Universidad Austral de Chile [PI14/00041, PI17/00119, PI14/00386, PI17/01495]
- Instituto de Salud Carlos III [PI14/00041, PI17/00119, PI14/00386, PI17/01495]
- FEDER European Union funds [PI14/00041, PI17/00119, PI14/00386, PI17/01495]
- Red de Investigacion Renal (REDinREN) [RD16/009]
- Comunidad de Madrid [B2017/BMD-3751 NOVELREN-CM]
- Sociedad Espanola de Nefrologia
- [PAI 82140017]
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Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect of IL-17A, the Th17 effector cytokine. Among experimental DN models, mouse strain BTBR ob/ob (leptin deficiency mutation) develops histological features similar to human DN, which means an opportunity to study mechanisms and novel therapies aimed at DN regression. We found that BTBR ob/ob mice presented renal activation of the factors controlling Th17 differentiation. The presence of IL-17A-expressing cells, mainly CD4(+) and gamma delta lymphocytes, was associated with upregulation of proinflammatory factors, macrophage infiltration and the beginning of renal damage. To study IL-17A involvement in experimental DN pathogenesis, treatment with an IL-17A neutralizing antibody was carried out starting when the renal damage had already appeared. IL-17A blockade ameliorated renal dysfunction and disease progression in BTBR ob/ob mice. These beneficial effects correlated to podocyte number restoration and inhibition of NF-kappa B/proinflammatory factors linked to a decrease in renal inflammatory-cell infiltration. These data demonstrate that IL-17A takes part in diabetes-mediated renal damage and could be a promising therapeutic target to improve DN.
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