Targeting the immunity-cell death axis: a multi-parametric network approach of traditional Chinese medicine against ischemia-reperfusion acute kidney injury
4 affiliations
- 1School of Integrative Medicine, Chongqing College of Traditional Chinese Medicine
- 2Department of Traditional Chinese Medicine, Health Center of Jinfeng Town, High-Tech Zone
- 3Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine
- 4The First Affiliated Hospital of Chongqing College of Traditional Chinese Medicine
Abstract
Acute kidney injury (AKI) remains a major clinical challenge, with persistently high incidence and mortality. Ischemia/reperfusion induced AKI (I/R-AKI) is the most common type, and its core pathological event is injury to renal tubular epithelial cells (RTECs). Energy depletion during ischemia and the burst of reactive oxygen species (ROS) during reperfusion induce metabolic reprogramming. These changes create a metabolic stress microenvironment and drive innate immune activation. This cascade begins with the release of damage-associated molecular patterns (DAMPs) and centers on sensing by pattern recognition receptors (PRRs). Macrophages then polarize toward the M1 phenotype and amplify inflammation, thereby constituting the “immunity–cell death axis.” During this process, multiple modalities of programmed cell death (PCD) interact with one another. These include apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy with dual roles. Together, they form a closely interconnected “death network,” which serves as the effector endpoint of the immune response described above. Given the extensive crosstalk within this network, interventions directed at a single death pathway have limited efficacy. Multitarget strategies that simultaneously address several key nodes are therefore emerging as a new research direction. On this basis, the present review systematically elucidates the molecular pathways of PCD in I/R-AKI and their immunoregulatory mechanisms. It also summarizes the potential mechanisms and recent advances of traditional Chinese medicine (TCM) in intervening in I/R-AKI through multipathway regulation of PCD. We hope this review provides a reference for further exploration and clinical translation in this field.
Related
- Senescent cells in cancer immunity: mechanisms of immune remodeling and opportunities for traditional Chinese medicine-derived senotherapeutics
- Unlocking the therapeutic potential of traditional Chinese medicine in Crohn’s disease: from multi-target mechanisms to clinical promise
- Fucoidan: Structure–activity relationships, molecular mechanisms, and nanotherapeutic applications with perspectives from Traditional Chinese Medicine
- Traditional Chinese medicine modulates immune homeostasis through the gut microbiota–microbial metabolite axis
- PANoptosis: a novel therapeutic target and mechanistic insight into traditional Chinese medicine intervention in inflammatory bowel disease: a review
BibTeX
@article{tang2026targeting,
title = {{Targeting the immunity-cell death axis: a multi-parametric network approach of traditional Chinese medicine against ischemia-reperfusion acute kidney injury}},
author = {Anqi Tang and Mingquan Li and Yudi Zhang and Kaiyue Tan},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1976812},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976812/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting the immunity-cell death axis: a multi-parametric network approach of traditional Chinese medicine against ischemia-reperfusion acute kidney injury
AU - Anqi Tang
AU - Mingquan Li
AU - Yudi Zhang
AU - Kaiyue Tan
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1976812
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976812/full
AB - Acute kidney injury (AKI) remains a major clinical challenge, with persistently high incidence and mortality. Ischemia/reperfusion induced AKI (I/R-AKI) is the most common type, and its core pathological event is injury to renal tubular epithelial cells (RTECs). Energy depletion during ischemia and the burst of reactive oxygen species (ROS) during reperfusion induce metabolic reprogramming. These changes create a metabolic stress microenvironment and drive innate immune activation. This cascade begins with the release of damage-associated molecular patterns (DAMPs) and centers on sensing by pattern recognition receptors (PRRs). Macrophages then polarize toward the M1 phenotype and amplify inflammation, thereby constituting the “immunity–cell death axis.” During this process, multiple modalities of programmed cell death (PCD) interact with one another. These include apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy with dual roles. Together, they form a closely interconnected “death network,” which serves as the effector endpoint of the immune response described above. Given the extensive crosstalk within this network, interventions directed at a single death pathway have limited efficacy. Multitarget strategies that simultaneously address several key nodes are therefore emerging as a new research direction. On this basis, the present review systematically elucidates the molecular pathways of PCD in I/R-AKI and their immunoregulatory mechanisms. It also summarizes the potential mechanisms and recent advances of traditional Chinese medicine (TCM) in intervening in I/R-AKI through multipathway regulation of PCD. We hope this review provides a reference for further exploration and clinical translation in this field.
SN - 1664-3224
ER -