Macrophage Phenotype in Kidney Injury and Repair

Abstract

Background: Glomerular and interstitial macrophage infiltration is a feature for both the acute and chronic kidney diseases. Macrophages have been shown to play a diverse role in kidney injury and repair. Thus, macrophages may be a key cell type in acute and chronic kidney injury and repair.

Summary and key messages: During renal inflammation, circulating monocytes are recruited and then become activated and polarized. By adapting to the local microenvironment, macrophages can differentiate into different phenotypes and function as a double-bladed sword in different stages of kidney disease. In general, M1 macrophages play a pathogenic role in boosting inflammatory renal injury, whereas M2 macrophages exert an anti-inflammatory and wound healing (or profibrotic) role during renal repair. In this review, we highlight the phenotypic polarization of macrophages in renal diseases and dissect their distinct functions in renal injury and repair processes, respectively. Moreover, the current understanding of regulatory mechanisms on the phenotypic switch and macrophage-related therapy are also intensively discussed.

Keywords: Fibrosis; Inflammation; Macrophage; Phenotype.

Fig. 1

Macrophage phenotypes in renal injury and repair. During renal inflammation, circulating monocytes are recruited into the injured kidney in response to chemokines released by immune cells and intrinsic kidney cells. Then, monocytes differentiate and polarize into macrophages with distinct phenotypes under the influence of local microenvironments. Th1 cytokines (such as IFN-γ and TNF-α) induce M1 macrophages, while Th2 cytokines (such as IL-4, IL-13, and IL-10) promote M2 polarization. Additionally, M1 can switch to M2 macrophages in the presence of Th2 cytokines or after engulfing apoptotic cells. M1 macrophages produce an abundance of proinflammatory cytokines (IL-1, IL-6, and TNF-α), iNOS, and ROS, therefore promoting renal injury. M2 macrophages can synthesize anti-inflammatory cytokines (such as IL-10 and TGF-β) and trophic factors (such as hepatocyte growth factor and IGF) to accelerate the resolution of inflammation and repair process. However, unresolved inflammation and uncontrolled wound healing processes can trigger the process of renal fibrosis by enhancing activation and differentiation of macrophages.