Macrophages: versatile players in renal inflammation and fibrosis
Abstract
Macrophages have important roles in immune surveillance and in the maintenance of kidney homeostasis; their response to renal injury varies enormously depending on the nature and duration of the insult. Macrophages can adopt a variety of phenotypes: at one extreme, M1 pro-inflammatory cells contribute to infection clearance but can also promote renal injury; at the other extreme, M2 anti-inflammatory cells have a reparative phenotype and can contribute to the resolution phase of the response to injury. In addition, bone marrow monocytes can differentiate into myeloid-derived suppressor cells that can regulate T cell immunity in the kidney. However, macrophages can also promote renal fibrosis, a major driver of progression to end-stage renal disease, and the CD206+ subset of M2 macrophages is strongly associated with renal fibrosis in both human and experimental diseases. Myofibroblasts are important contributors to renal fibrosis and recent studies provide evidence that macrophages recruited from the bone marrow can transition directly into myofibroblasts within the injured kidney. This process is termed macrophage-to-myofibroblast transition (MMT) and is driven by transforming growth factor-β1 (TGFβ1)-Smad3 signalling via a Src-centric regulatory network. MMT may serve as a key checkpoint for the progression of chronic inflammation into pathogenic fibrosis.
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There is increasing evidence that local intrarenal macrophages and infiltrating macrophages produce cytokines and chemokines that can create a feed-forward cycle to accelerate intrarenal inflammation in various kidney diseases, including diabetes.
“There is also increasing evidence that these two macrophage populations produce cytokines and chemokines that can create a feed-forward cycle to accelerate intrarenal inflammation in various kidney diseases, including in diabetes (65).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [65]
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- Authors
- Tang, P. M.-K., Nikolic-Paterson, D. J., & Lan, H.-Y.
- Affiliations
- Chinese University of Hong Kong (HK)
- Corresponding author
- Lan, Hui-Yao
- Venue
- Nature Reviews Nephrology
- Published
- 2019-01-28
- Volume
- 15
- Issue
- 3
- Pages
- 144-158
- ISSN
- 1745-8323 (ISSN-L)
- 1759-5061
- 1759-507X
- OpenAlex
- W2913590717
- Cited by
- 1,033
- References
- 6
- Citations by year
- 2026: 140 · 2025: 190 · 2024: 188 · 2023: 141 · 2022: 153 · 2021: 126 · 2020: 69 · 2019: 25
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- macrophages, renal inflammation, renal fibrosis, M1 macrophages, M2 macrophages, myeloid-derived suppressor cells, CD206+ macrophages, myofibroblast differentiation, macrophage-to-myofibroblast transition, chronic kidney disease, end-stage renal disease, bone marrow-derived monocytes, kidney homeostasis
- MeSH terms
- Animals, Fibrosis, Humans, Immunity, Cellular, Kidney Diseases, Macrophages, Nephritis, Signal Transduction, Disease Progression
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