Division of Nephrology, Duke University and Durham VA Medical Centers, Durham, North Carolina, USA.
Curr Opin Nephrol Hypertens. 2020 May;29(3):286-292. doi: 10.1097/MNH.0000000000000595.
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.
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.
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.
巨噬细胞在调节体内平衡、肾损伤、修复和组织纤维化方面发挥着重要作用。本综述将讨论探索肾脏损伤和高血压发病机制中巨噬细胞新亚群和功能的最新进展。
巨噬细胞在依赖于微环境的方式下分化为多种亚群。尽管 M1/M2 命名法仍用于考虑巨噬细胞在肾损伤中的促炎与抗炎作用，但通过流式细胞术标记和单细胞 RNA 特征可定义新型且准确的巨噬细胞表型。随着细胞间外泌体转运的进一步认识，探索巨噬细胞与其他细胞之间相互作用的研究正在迅速推进。利用鼠条件性突变体，可比骨髓转移模型更精确地定义巨噬细胞的作用。一些研究揭示了同一蛋白在肾实质细胞和巨噬细胞中的相反作用，这凸显了开发针对特定细胞的免疫治疗以促进转化的必要性。
针对巨噬细胞的治疗方法有望限制肾损伤和高血压。为了实现这一潜力，未来的研究将需要深入了解肾脏疾病中巨噬细胞极化、相互作用、增殖和成熟的精确机制。
