Depletion of miR‐21 in dendritic cells aggravates renal ischemia‐reperfusion injury

Abstract

Abstract Dendritic cells (DCs) play an important role in the pathophysiology of renal ischemia‐reperfusion injury (IRI). The mechanisms underlying DCs phenotypic modulation and their function are not fully understood. In this study, we examined the effect of miR‐21 on the phenotypic modulation of DCs in vitro and in vivo, and further investigated the impact of miR‐21‐overexpression DC or miR‐21‐deficient DC on renal IRI. We found that treatment with hypoxia/reoxygenation (H/R) suppressed miR‐21 expression in bone marrow‐derived dendritic cells (BMDCs), and significantly increased the percentage of mature DCs (CD11c + /MHC‐II + /CD80 + ). Using a selection of microRNA mimics, we successfully induced the upregulation of miR‐21 in BMDCs, which induced immature DC phenotype and an anti‐inflammatory DC response. However, deletion of miR‐21 in BMDCs promoted maturation of DCs under H/R. Adoptive transfer of miR‐21‐overexpression BMDCs could alleviate renal IR‐induced pro‐inflammatory cytokines production and acute kidney injury (AKI). Mice with miR‐21 deficiency in DCs subjected to renal IR showed more severe renal dysfunction and inflammatory response compared with wild‐type mice. In addition, chemokine C receptor 7 (CCR7), a surface marker of mature DC, was a target gene of miR‐21, and silencing of CCR7 in BMDCs led to reduced mature DCs under H/R. In conclusion, our findings highlight miR‐21 as a key regulator of DCs subset phenotype and a potential therapeutic target in renal IRI.