Macrophage heterogeneity, phenotypes, and roles in renal fibrosis

Abstract

Macrophages (MΦ) are highly heterogeneous cells that exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. MΦ are distributed throughout normal and diseased kidney tissue, where they have been recognized as key factors in renal fibrosis. Recent studies have identified switch of phenotype and diverse roles for MΦ in several murine models of kidney disease. In this review, we discuss macrophage heterogeneity and their involvement in renal fibrosis.

Keywords: effector; fibrosis; macrophages; regulatory.

Figure 1

Macrophage phenotype and function are critical determinants of kidney fibrosis. In response to ongoing injury, activated pro-inflammatory macrophages (M1) enhance kidney inflammation by secreting pathogenic mediators, resulting in kidney fibrosis in the late stage of disease. M1 macrophages also directly induce kidney fibrosis by secreting profibrotic factors, such as matrix metalloprotease (MMP)-9. In contrast, anti-inflammatory macrophages (M2) suppress kidney inflammation by releasing anti-inflammatory mediators interleukin (IL)-10 and transforming growth factor-beta (TGF-β), resulting in reduced kidney fibrosis. In addition, TGF-β produced by M2 macrophages promotes kidney fibrosis directly. Therefore, the net effect of M2 macrophages on kidney fibrosis is uncertain. CCL2, chemokine ligand 2; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-alpha.