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Review
. 2019 Dec 1;317(6):F1409-F1413.
doi: 10.1152/ajprenal.00380.2019. Epub 2019 Sep 30.

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

Jason E Engel  1 , Alejandro R Chade  1   2   3
Affiliations
Review

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

Jason E Engel et al. Am J Physiol Renal Physiol. .

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.

Keywords: chronic kidney disease; fibrosis; inflammation; macrophages; tissue repair.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
A schematic overview of macrophages in progression of renal injury. The initial renal damage leads to the release of chemotactic factors, inducing macrophage infiltration and subsequent differentiation to the M1 phenotype. M1 macrophages release multiple inflammatory cytokines, which drive tubular injury, endothelial dysfunction, and inflammation, leading to fibrosis and progression of renal injury toward chronic kidney disease (CKD) if left unchecked. In the normal course of healing, macrophages shift to the M2 phenotype and participate in the repair process through production of VEGF and Wnt7b (favoring microvascular recovery and parenchymal regeneration respectively, red lines) and surface expression of mannose receptor C type 2 (MRC2) to reduce the progression of fibrosis (red lines) and stimulate fibrolysis. M2 differentiation is favored by polarizing factors produced by M1 macrophages, such as IL-1 receptor-associated kinase M (IRAK-M), and inhibited by persistent inflammation favoring M1 polarization. Modulation of macrophage function or polarization state by genetic or cytokine approaches (*potential therapeutic targets) offers new potential therapeutic strategies for improving outcomes in kidney disease. DAMP, damage-associated molecular patterns.
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References

    1. Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif 39: 84–92, 2015. doi:10.1159/000368940. - DOI - PubMed
    1. Amano MT, Castoldi A, Andrade-Oliveira V, Latancia MT, Terra FF, Correa-Costa M, Breda CNS, Felizardo RJF, Pereira WO, da Silva MB, Miyagi MYS, Aguiar CF, Hiyane MI, Silva JS, Moura IC, Camara NOS. The lack of PI3Kγ favors M1 macrophage polarization and does not prevent kidney diseases progression. Int Immunopharmacol 64: 151–161, 2018. doi:10.1016/j.intimp.2018.08.020. - DOI - PubMed
    1. Boyce NW, Tipping PG, Holdsworth SR. Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis. Kidney Int 35: 778–782, 1989. doi:10.1038/ki.1989.52. - DOI - PubMed
    1. Braga TT, Correa-Costa M, Guise YF, Castoldi A, de Oliveira CD, Hyane MI, Cenedeze MA, Teixeira SA, Muscara MN, Perez KR, Cuccovia IM, Pacheco-Silva A, Gonçalves GM, Camara NO. MyD88 signaling pathway is involved in renal fibrosis by favoring a TH2 immune response and activating alternative M2 macrophages. Mol Med 18: 1231–1239, 2012. doi:10.2119/molmed.2012.00131. - DOI - PMC - PubMed
    1. Cao Q, Wang Y, Zheng D, Sun Y, Wang Y, Lee VW, Zheng G, Tan TK, Ince J, Alexander SI, Harris DC. IL-10/TGFβ-modified macrophages induce regulatory T cells and protect against adriamycin nephrosis. J Am Soc Nephrol 21: 933–942, 2010. doi:10.1681/ASN.2009060592. - DOI - PMC - PubMed

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