Targeting the immunity-cell death axis: a multi-parametric network approach of traditional Chinese medicine against ischemia-reperfusion acute kidney injury
Year: 2026
Type: review
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.
Source: Frontiers in Immunology
Authors: Anqi Tang, Mingquan Li, Yudi Zhang, Kaiyue Tan
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G7772057222
OpenAlex ID: W7222931461