Yi Wen1, Steven D Crowley. 1. Division of Nephrology, Duke University and Durham VA Medical Centers, Durham, North Carolina, USA.
Abstract
PURPOSE OF REVIEW: Macrophages play an important role in regulating homeostasis, kidney injury, repair, and tissue fibrogenesis. The present review will discuss recent advances that explore the novel subsets and functions of macrophage in the pathogenesis of kidney damage and hypertension. RECENT FINDINGS: Macrophages differentiate into a variety of subsets in microenvironment-dependent manner. Although the M1/M2 nomenclature is still applied in considering the pro-inflammatory versus anti-inflammatory effects of macrophages in kidney injury, novel, and accurate macrophage phenotypes are defined by flow cytometric markers and single-cell RNA signatures. Studies exploring the crosstalk between macrophages and other cells are rapidly advancing with the additional recognition of exosome trafficking between cells. Using murine conditional mutants, actions of macrophage can be defined more precisely than in bone marrow transfer models. Some studies revealed the opposing effects of the same protein in renal parenchymal cells and macrophages, highlighting a need for the development of cell-specific immune therapies for translation. SUMMARY: Macrophage-targeted therapies hold potential for limiting kidney injury and hypertension. To realize this potential, future studies will be required to understand precise mechanisms in macrophage polarization, crosstalk, proliferation, and maturation in the setting of renal disease.
PURPOSE OF REVIEW: Macrophages play an important role in regulating homeostasis, kidney injury, repair, and tissue fibrogenesis. The present review will discuss recent advances that explore the novel subsets and functions of macrophage in the pathogenesis of kidney damage and hypertension. RECENT FINDINGS: Macrophages differentiate into a variety of subsets in microenvironment-dependent manner. Although the M1/M2 nomenclature is still applied in considering the pro-inflammatory versus anti-inflammatory effects of macrophages in kidney injury, novel, and accurate macrophage phenotypes are defined by flow cytometric markers and single-cell RNA signatures. Studies exploring the crosstalk between macrophages and other cells are rapidly advancing with the additional recognition of exosome trafficking between cells. Using murine conditional mutants, actions of macrophage can be defined more precisely than in bone marrow transfer models. Some studies revealed the opposing effects of the same protein in renal parenchymal cells and macrophages, highlighting a need for the development of cell-specific immune therapies for translation. SUMMARY: Macrophage-targeted therapies hold potential for limiting kidney injury and hypertension. To realize this potential, future studies will be required to understand precise mechanisms in macrophage polarization, crosstalk, proliferation, and maturation in the setting of renal disease.
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