Macrophage polarization in chronic kidney disease: a balancing act between renal recovery and decline?

Abstract

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments, where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a proinflammatory M1 phenotype. Later in the course of healing, abundant apoptotic debris and anti-inflammatory cytokines induce the production of anti-inflammatory M2 macrophages, which contribute to tissue regeneration and repair. Thus, the dynamic balance of M1 and M2 populations may outline the burden of inflammation and process of tissue repair that define renal outcomes, which has been the impetus for therapeutic efforts targeting macrophages. This review will discuss the role of these phenotypes in the progression of chronic renal injury, potential pathogenic mechanisms, and the promise of macrophage-based therapeutic applications for chronic kidney disease.

Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys

“…All these functions of CLU in the TEC may contribute to the tubular repair we have observed. Furthermore, M2 Mφ and other anti‐inflammatory mediators may promote the intrinsic regeneration of remnant tubules to replace at least some of the necrotic cells 39,40 …”

“…Furthermore, M2 Mφ and other antiinflammatory mediators may promote the intrinsic regeneration of remnant tubules to replace at least some of the necrotic cells. 39,40 Only a few tissue-resident Mφ are present in na€ ıve kidneys. However, following acute kidney injury, the monocytes were effectively recruited to the injured kidney to differentiate into Mφ, and the number of M1 Mφ peaked at day 3 and declined afterward.…”

Regulating the Polarization of Macrophages: A Promising Approach to Vascular Dermatosis

“…With the maturation of the innate immune system, the M1/M2 population tends to balance and maintains body homeostasis [ 34 ]. In pathological conditions, however, when inflammation occurs, vascular tissue is the major response place where macrophages have a switch from M1 to M2 [ 35 ]. M1 actively participates in the initial process of vascular inflammation, which benefits to the establishment of a proinflammatory response.…”

“…If M1 phase persistently exists, tissue damage would occur. Instead, the sequential presence of M2 macrophages facilitates damage termination and tissue repair in the later phase [ 35 , 36 ]. However, in many vascular disorders especially in vascular dermatosis, the vascular microenvironment fills with various inflammatory mediators from infiltrated lymphocytes and resident parenchymal cells.…”

Macrophage polarization in innate immune responses contributing to pathogenesis of chronic kidney disease

“…Chronic kidney disease (CKD) bears a major global health burden, with an estimated prevalence of 8 to 16% of the population worldwide [ 1 , 2 ]. CKD is manifested by chronic inflammation, with sustained, unsuccessful injury-repair cycles and subsequent fibrosis [ 3 ] and these processes involve both protective and pathogenic roles of macrophages [ 3 ].…”