Innate immunity: current understandings and future perspectives
6 affiliations
- 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- 2Department of Hematology and Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China
- 3State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected]
- 4Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. [email protected]
- 5Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, China. [email protected]
- 6Laboratory of Pathogen Research, West China Hospital, Sichuan University, Chengdu, China. [email protected]
Abstract
Innate immunity constitutes the body's first line of defense, deploying evolutionarily conserved mechanisms to detect and respond to pathogenic threats and tissue injury. In contrast to the adaptive immune system's specificity and memory, innate immunity relies on germline-encoded pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). This review outlines the major PRR families and their downstream signaling pathways, culminating in the production of cytokines and inflammasome activation. Additionally, this review explores the functional integration of cellular responses and examines the sophisticated regulatory circuits, including transcriptional, posttranscriptional, epigenetic, and metabolic mechanisms, that calibrate innate immune responses. Importantly, we highlight how dysregulated innate immunity underlies a wide spectrum of diseases, from autoinflammatory and autoimmune disorders to chronic inflammatory states and cancer. Recent insights into trained immunity and innate immune memory further redefine the scope of innate defenses, revealing that metabolic and epigenetic remodeling can prime innate cells for enhanced secondary responses. Finally, we discuss the therapeutic potential of modulating innate pathways, including PRR agonists as vaccine adjuvants or anticancer agents, and PRR inhibitors in autoimmune and inflammatory diseases. By integrating current mechanistic knowledge with emerging therapeutic strategies, this review underscores the central role of innate immunity in health and disease while pointing toward promising avenues for future research and clinical translation.
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BibTeX
@article{zou2026innate,
title = {{Innate immunity: current understandings and future perspectives}},
author = {Chaoyu Zou and Teng Ma and Jing Li and Xikun Zhou},
journal = {Signal Transduction and Targeted Therapy},
year = {2026},
month = aug,
doi = {10.1038/s41392-026-02920-0},
url = {https://doi.org/10.1038/s41392-026-02920-0},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Innate immunity: current understandings and future perspectives
AU - Chaoyu Zou
AU - Teng Ma
AU - Jing Li
AU - Xikun Zhou
PY - 2026
DA - 2026/08/12
JO - Signal Transduction and Targeted Therapy
DO - 10.1038/s41392-026-02920-0
UR - https://doi.org/10.1038/s41392-026-02920-0
AB - Innate immunity constitutes the body's first line of defense, deploying evolutionarily conserved mechanisms to detect and respond to pathogenic threats and tissue injury. In contrast to the adaptive immune system's specificity and memory, innate immunity relies on germline-encoded pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). This review outlines the major PRR families and their downstream signaling pathways, culminating in the production of cytokines and inflammasome activation. Additionally, this review explores the functional integration of cellular responses and examines the sophisticated regulatory circuits, including transcriptional, posttranscriptional, epigenetic, and metabolic mechanisms, that calibrate innate immune responses. Importantly, we highlight how dysregulated innate immunity underlies a wide spectrum of diseases, from autoinflammatory and autoimmune disorders to chronic inflammatory states and cancer. Recent insights into trained immunity and innate immune memory further redefine the scope of innate defenses, revealing that metabolic and epigenetic remodeling can prime innate cells for enhanced secondary responses. Finally, we discuss the therapeutic potential of modulating innate pathways, including PRR agonists as vaccine adjuvants or anticancer agents, and PRR inhibitors in autoimmune and inflammatory diseases. By integrating current mechanistic knowledge with emerging therapeutic strategies, this review underscores the central role of innate immunity in health and disease while pointing toward promising avenues for future research and clinical translation.
SN - 2059-3635
SN - 2095-9907
ER -