Abstract
Chronic kidney disease (CKD) is characterized by inflammation, injury and fibrosis. Dysregulated innate immune responses mediated by macrophages play critical roles in progressive renal injury. The differentiation and polarization of macrophages into pro-inflammatory ‘M1’ and anti-inflammatory ‘M2’ states represent the two extreme maturation programs of macrophages during tissue injury. However, the effects of macrophage polarization on the pathogenesis of CKD are not fully understood. In this review, we discuss the innate immune mechanisms underlying macrophage polarization and the role of macrophage polarization in the initiation, progression, resolution and recurrence of CKD. Macrophage activation and polarization are initiated through recognition of conserved endogenous and exogenous molecular motifs by pattern recognition receptors, chiefly, Toll-like receptors (TLRs), which are located on the cell surface and in endosomes, and NLR inflammasomes, which are positioned in the cytosol. Recent data suggest that genetic variants of the innate immune molecule apolipoprotein L1 (APOL1) that are associated with increased CKD prevalence in people of African descent, mediate an atypical M1 macrophage polarization. Manipulation of macrophage polarization may offer novel strategies to address dysregulated immunometabolism and may provide a complementary approach along with current podocentric treatment for glomerular diseases.
Highlights
Macrophage polarization and chronic kidney diseases Chronic inflammation plays a leading role in the progression of Chronic kidney disease (CKD)
Innate responses involve non-specific immune functions that are induced upon detection of pathogen-associated molecular patterns (PAMPs [e.g., bacterial lipopolysaccharide]) and hostderived damage-associated molecular patterns (DAMPs [e.g., mitochondrial DNA]) by pattern recognition receptors (PRRs), [4] of which the best studied in association with CKD are membrane-bound Toll-like receptors
M1 macrophages are typically induced by exposure to interferon-γ and/or lipopolysaccharide and are considered pro-inflammatory, while M2 macrophages are induced by interleukins (IL) like IL-4, IL-13, and IL-33, and are considered antiinflammatory [7, 8], which can be further subcategorized into three subgroups: M2a macrophages are induced by IL-4 and/or IL-13, induce anti-inflammatory, wound healing and tissue fibrosis; M2b macrophages are induced by immune complexes in combination of LPS and/or IL-1 receptor (IL-1R) ligands, function in immunoregulation; M2c macrophages are induced by IL-10, transforming growth factor (TGF)-β or glucocorticoids, contribute to immunosuppression, matrix deposition and tissue remodeling [7, 8]
Summary
Chronic kidney disease (CKD) bears a major global health burden, with an estimated prevalence of 8 to 16% of the population worldwide [1, 2]. M1 macrophages are typically induced by exposure to interferon-γ and/or lipopolysaccharide and are considered pro-inflammatory, while M2 macrophages are induced by interleukins (IL) like IL-4, IL-13, and IL-33, and are considered antiinflammatory [7, 8], which can be further subcategorized into three subgroups: M2a macrophages are induced by IL-4 and/or IL-13, induce anti-inflammatory, wound healing and tissue fibrosis; M2b macrophages are induced by immune complexes in combination of LPS and/or IL-1R ligands, function in immunoregulation; M2c macrophages are induced by IL-10, transforming growth factor (TGF)-β or glucocorticoids, contribute to immunosuppression, matrix deposition and tissue remodeling [7, 8] As these pure in vitro stimulation conditions are somewhat artificial and reductionist, it is generally recognized that the M1 and M2/M2 subset states are largely idealized and that macrophage polarization in vivo is much more complex, characterized by a continuum of functional phenotypes. It is an over-simplification this review will use the ‘M1’ and ‘M2’ dichotomy terminology, in most cases, to align with the existing literature and distinct Th1 and Th2 adaptive immune system of which macrophages is associated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
