Lian YJ, Li MY, Wang L, Gao YW, Zhu D, Lyu WL. Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications. World J Gastroenterol 2026; 32(43): 121310 [DOI: 10.3748/wjg.121310]
Corresponding Author of This Article
Wen-Liang Lyu, PhD, Professor, Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China. lvwenliang2892@gamyy.cn
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Gastroenterology & Hepatology
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review-article
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Lian YJ, Li MY, Wang L, Gao YW, Zhu D, Lyu WL. Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications. World J Gastroenterol 2026; 32(43): 121310 [DOI: 10.3748/wjg.121310]
World J Gastroenterol. Nov 21, 2026; 32(43): 121310 Published online Nov 21, 2026. doi: 10.3748/wjg.121310
Crosstalk between neutrophils and hepatic stellate cells in liver injury and repair: Mechanisms and implications
Yan-Jie Lian, Ming-Yang Li, Li Wang, Yu-Wen Gao, Dan Zhu, Wen-Liang Lyu
Yan-Jie Lian, Dan Zhu, Wen-Liang Lyu, Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Ming-Yang Li, College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Li Wang, Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Yu-Wen Gao, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
Co-first authors: Yan-Jie Lian and Ming-Yang Li.
Co-corresponding authors: Dan Zhu and Wen-Liang Lyu.
Author contributions: Lian YJ and Li MY should be considered co-first authors, because they contribute significantly to the manuscript in several key areas, including paper selection, literature collection, and manuscript composition. Lian YJ, Li MY, Wang L, Gao YW reviewed and edited the manuscript; Zhu D and Lyu WL should be considered co-corresponding authors. They have made significant contributions to the article by guiding the literature analysis and drafting the content. All authors have read and approved the final manuscript.
AI contribution statement: AI tools (specifically ChatGPT) were used solely for language polishing and structural optimization. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by High Level Chinese Medical Hospital Promotion Project, No. HLCMHPP2023086; and the Fundamental Research Funds for the Central Public Welfare Research Institutes, No. ZZ19-XRZ-045.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Wen-Liang Lyu, PhD, Professor, Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China. lvwenliang2892@gamyy.cn
Received: March 23, 2026 Revised: April 30, 2026 Accepted: June 15, 2026 Published online: November 21, 2026 Processing time: 189 Days and 16.5 Hours
Abstract
The liver has a remarkable capacity for regeneration; however, persistent or dysregulated inflammation can impair tissue repair, thereby promoting chronic fibrosis and, ultimately, cirrhosis. Neutrophils and hepatic stellate cells (HSCs) are key mediators of this pathological transition. Beyond the traditional view of neutrophils as short-lived effectors of tissue injury, accumulating evidence indicates that they exhibit marked plasticity and can adopt either pro-inflammatory or pro-repair phenotypes depending on the microenvironment. Recent studies have revealed a dynamic and bidirectional communication network between neutrophils and HSCs that regulates injury severity, resolution of inflammation, tissue repair, and fibrotic progression. This review summarizes the mechanistic evidence for neutrophils-HSCs crosstalk, with a focus on the following aspects: (1) Initiating soluble mediators, including reactive oxygen species, proteases, and cytokines; (2) Signal amplification through extracellular matrix remodeling and mechanotransduction; and (3) The role of neutrophil extracellular traps as a signaling platform that sustains profibrotic programs. In addition, the review highlights how temporal factors and disease context determine whether this crosstalk facilitates regenerative repair or evolves into a self-amplifying fibrotic circuit. Finally, translational opportunities are discussed, and it is proposed that next-generation antifibrotic strategies should prioritize phase-specific and precision-based remodeling of key regulatory nodes.
Core Tip: Crosstalk between neutrophils and hepatic stellate cells is a crucial regulatory axis that determines whether liver injury resolves or progresses to fibrosis. This interaction is highly context- and stage-dependent. During acute injury, it triggers transient reparative signaling; however, in diseases such as metabolic dysfunction-associated steatohepatitis, liver cirrhosis, and hepatocellular carcinoma, it promotes persistent pathological activation. Targeting specific nodes within this crosstalk (e.g., neutrophil extracellular traps, NOD-like receptor family pyrin domain containing 3, transforming growth factor-β) enables a precision-remodeling strategy, offering stage-specific anti-fibrotic interventions while preserving essential immune repair functions.
