CD11b deficiency attenuates the ischemia/reperfusion-induced AKI-to-CKD process by regulatingmacrophage polarization.

Abstract

Severe acute kidney injury (AKI) is a risk factor for the future development of chronic kidney disease (CKD), and macrophages are an essential cell group implicated in injury, repair, and fibrosis during this progress. However, the underlying mechanism of how macrophages participate in the development of the disease is largely unclear. CD11b (Integrin αM) is highly expressed in monocytes/macrophages and has been verified to mediate broad functions. We found that CD11b-knockout mice were protected from the ischemia/reperfusion-induced AKI-to-CKD process. Additionally, renal macrophages from the kidneys of CD11b-deficient mice presented an M2-like, anti-inflammatory phenotype. We demonstrated both invitro and invivo that enhanced alternative activation in CD11b-knockout macrophages is regulated by the interleukin (IL)-4/signal transducer and activator of transcription (STAT) 6 axis, which is mediated by the inactivation of the Src-family kinase (SFK) member Lyn. Importantly, the therapeutical administration of CD11b-neutralizing antibody can effectively prevent AKI-to-CKD progress. Thus, our study verifies that CD11b plays a critical role in limiting the alternative activation of macrophages and may be a potential therapeutic target during the AKI-to-CKD process.