Role of prolyl-hydroxylase domain enzyme inhibitors in chronic renal inflammation (B05)

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Inhibition of prolyl hydroxylase domain enzymes (PHDi) protects mice in a model of chronic tubulointerstitial inflammasome-dependent kidney disease. PHDi-mediated protection required the presence of mononuclear phagocytes. Moreover, PHDi blocked caspase-1-dependent IL-1β release in mononuclear phagocytes. In order to test whether PHDi in mononuclear phagocytes ameliorates chronic nephritis we will characterize and analyze the contribution of subsets of mononuclear phagocytes in the pathogenesis of chronic inflammatory kidney diseases and their role in PHDi-mediated protection. Moreover, we will decipher how PHDi-treatment impairs IL-1β release in mononuclear phagocytes.