REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1642525
This article is part of the Research TopicDeciphering Macrophage Polarization/Transition in Human Inflammatory Disease and CancerView all 6 articles
The Multifaceted Role of Macrophages in Kidney Physiology and Diseases
Provisionally accepted
- 1Department of Radiology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China
- 2School of Medical Imaging, Hangzhou Medical College, Hangzhou, China
- 3Department of Nephrology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Zhejiang-Denmark Joint Laboratory of Regeneration and Aging Medicine, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China
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Macrophages are highly plastic and heterogeneous innate immune cells that play pivotal roles in kidney development, kidney functions maintenance, immune surveillance, injury, repair, fibrosis and so on. Our understanding of embryonic derived and bone marrow–derived macrophages has evolved beyond the classical M1/M2 polarization paradigm, shifting toward a more nuanced investigation of macrophage subpopulations through the lens of functional specialization and tissue-specific adaptation. Recent advancements in single-cell and spatial transcriptomics have elucidated the diversity of kidney macrophages, revealing their critical contribution to kidney physiology and pathology. In acute kidney injury, macrophages orchestrate inflammatory cascades via cytokine secretion and inflammasome activation, whereas during the reparative phase, they promote tissue regeneration through anti-inflammatory pathways. However, persistent or dysregulated macrophage activation can lead to maladaptive repair and progression to chronic kidney disease characterized by kidney fibrosis. Therapeutically, targeting macrophage polarization, recruitment and macrophage-based adoptive cell therapy has emerged as a promising strategy for modulating kidney inflammation and fibrosis. This review delineates the multifaceted roles of diverse macrophage subsets in kidney physiology and pathology, while highlighting emerging therapeutic avenues and the translational challenges associated with macrophage-targeted interventions.
Keywords: Macrophage heterogeneity, kidney physiology, Acute Kidney Injury, Chronic Kidney Disease, Sing-cell
Received: 06 Jun 2025; Accepted: 03 Sep 2025.
Copyright: © 2025 Ma, Yang, Yang, Wang, HU and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
JI BO HU, Department of Radiology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China
Qian Wu, Department of Radiology, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China
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