Extracellular vesicle–cytokine communication in diabetic kidney disease: an integrated network linking renal resident cells and macrophages
5 affiliations
- 1Dongzhimen Hospital, Beijing University of Chinese Medicine
- 2Sunsimiao Hospital, Beijing University of Chinese Medicine
- 3Department of Endocrinology, The Affiliated Hospital of Jiangxi University of Chinese Medicine (Jiangxi Provincial Hospital of Traditional Chinese Medicine)
- 4The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)
- 5Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine
Abstract
Chronic inflammation contributes to the onset and progression of diabetic kidney disease (DKD), yet a model centered solely on soluble cytokines does not fully explain the cellular origin, spatially directed delivery, or sustained amplification of local signals. Extracellular vesicles (EVs) couple vesicular signaling with cytokine regulation through EV-associated cytokine or ligand signals and through RNA or protein cargo that reprograms cytokine production in recipient cells. This review examines how metabolic stress alters EV release and cargo composition, summarizes evidence for unidirectional and bidirectional communication between resident kidney cells and immune cells, and evaluates the EV specificity and evidential completeness of each donor–recipient axis. Evidence is strongest for communication between tubular epithelial cells and macrophages; findings involving podocytes, mesangial cells, and glomerular endothelial cells are largely unidirectional or inferred across studies. Under the in vitro polarization conditions used in the source studies, EVs from macrophages polarized toward a pro-inflammatory phenotype generally promote injury, whereas some EVs from macrophages polarized toward a reparative phenotype limit cell damage or improve autophagy. On this basis, we propose an EV-associated inflammatory communication network linked by shared inflammatory endpoints and inferred return signals. Within this network, we propose that injury-promoting and protective signals compete dynamically and thereby influence persistent inflammation and fibrosis-related disease progression. This hypothesis integrates existing evidence and offers a framework for understanding persistent inflammation in DKD and for testing therapies that target intercellular communication.
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BibTeX
@article{guo2026extracellular,
title = {{Extracellular vesicle–cytokine communication in diabetic kidney disease: an integrated network linking renal resident cells and macrophages}},
author = {Zhixun Guo and Xinying Si and Zhichao Ruan and Jiangteng Liu and Nan Tong and Ying Tang and Yixin Ma and Dongchen Yang and Weijun Huang and Jinxi Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1967300},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967300/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular vesicle–cytokine communication in diabetic kidney disease: an integrated network linking renal resident cells and macrophages
AU - Zhixun Guo
AU - Xinying Si
AU - Zhichao Ruan
AU - Jiangteng Liu
AU - Nan Tong
AU - Ying Tang
AU - Yixin Ma
AU - Dongchen Yang
AU - Weijun Huang
AU - Jinxi Zhao
PY - 2026
DA - 2026/10/08
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1967300
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967300/full
AB - Chronic inflammation contributes to the onset and progression of diabetic kidney disease (DKD), yet a model centered solely on soluble cytokines does not fully explain the cellular origin, spatially directed delivery, or sustained amplification of local signals. Extracellular vesicles (EVs) couple vesicular signaling with cytokine regulation through EV-associated cytokine or ligand signals and through RNA or protein cargo that reprograms cytokine production in recipient cells. This review examines how metabolic stress alters EV release and cargo composition, summarizes evidence for unidirectional and bidirectional communication between resident kidney cells and immune cells, and evaluates the EV specificity and evidential completeness of each donor–recipient axis. Evidence is strongest for communication between tubular epithelial cells and macrophages; findings involving podocytes, mesangial cells, and glomerular endothelial cells are largely unidirectional or inferred across studies. Under the in vitro polarization conditions used in the source studies, EVs from macrophages polarized toward a pro-inflammatory phenotype generally promote injury, whereas some EVs from macrophages polarized toward a reparative phenotype limit cell damage or improve autophagy. On this basis, we propose an EV-associated inflammatory communication network linked by shared inflammatory endpoints and inferred return signals. Within this network, we propose that injury-promoting and protective signals compete dynamically and thereby influence persistent inflammation and fibrosis-related disease progression. This hypothesis integrates existing evidence and offers a framework for understanding persistent inflammation in DKD and for testing therapies that target intercellular communication.
SN - 1664-3224
ER -