MiR-142 inhibits cecal ligation and puncture (CLP)-induced inflammation via inhibiting PD-L1 expression in macrophages and improves survival in septic mice

Abstract

This study aims to explore the roles of miR-142/PD-L1 axis in cecal ligation and puncture (CLP)-induced inflammation and the survival in septic mice. Here, miR-142 was found to be decreased in sepsis patients. And miR-142 was decreased but PD-L1 was increased in CLP-treated mice macrophages in a time-dependent manner. Mechanistically, miR-142/PD-L1 regulatory axis was identified in macrophages. Pre-injection of miR-142 agomir following CLP treatment attenuated CLP-induced inflammation, characterized as the downregulation of IL-2 and TNF-α secretion, but this effect could not be ameliorated by post-injection of miR-142 agomir after CLP treatment. Additionally, PD-L1 overexpression enhanced CLP-induced inflammation and reversed miR-142-mediated inhibition on CLP-induced inflammation in macrophages. Importantly, CD4+T/CD8+T cell ratio was markedly increased in the peripheral blood of CLP-treated mice, which was attenuated by pre-injection of miR-142 agomir. Moreover, pre-injection of miR-142 agomir or aPD-L1 decreased CLP-induced mortality. Therefore, our results indicate that miR-142 could attenuate CLP-induced inflammation and thus sepsis via targeting PD-L1 in macrophages.

Keywords: CLP; Immunosuppression; PD-L1; Sepsis; miR-142.