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Hepatic Stellate Cells Interact with the Immune System: A Bidirectional Crosstalk Network Driving Liver Fibrosis

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Hepatic Stellate Cells Interact with the Immune System: A Bidirectional Crosstalk Network Driving Liver Fibrosis

Chu-Ning Zhang 1,2 Guan-Yue Shan 1,3 Hui Wan 1,2 Yu-Xin Zhang 1,2 Zhi-Cheng Gao 1,2 Hai-Jun Li 1,2,4,*

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1
Laboratory for Tumor Immunology, The First Hospital of Jilin University, Changchun 130061, China
2
Institute of Ginseng Research, Jilin University, Changchun 130021, China
3
Department of Bioengineering, Jilin University School of Pharmaceutical Sciences, Changchun 130021, China
4
China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, The First Hospital of Jilin University, Changchun 130021, China
*
Authors to whom correspondence should be addressed.

Received: 28 January 2026 Revised: 24 February 2026 Accepted: 31 March 2026 Published: 10 April 2026

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© 2026 The authors. This is an open access article under the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

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Fibrosis 2026, 4(2), 10006; DOI: 10.70322/fibrosis.2026.10006
ABSTRACT: As a central metabolic and immune organ, the liver maintains a unique immune microenvironment which is crucial for sustaining health. When the immune balance in the liver is disrupted, it can drive the occurrence and progression of various chronic liver diseases, including liver fibrosis. Hepatic stellate cells (HSCs) are the key effector cells responsible for producing extracellular matrix (ECM) during liver fibrosis, and the hepatic immune microenvironment precisely regulates their activation. This review focuses on the complex bidirectional interaction network between HSCs and major immune cells in the liver, including macrophages, natural killer (NK) cells, and T cells. It systematically elucidates the central role of these interactions in maintaining hepatic homeostasis, mediating inflammatory responses, and driving the progression of fibrosis. A deeper understanding of the interaction between HSCs and immune cells is essential for elucidating the pathological mechanisms of liver fibrosis and will provide a theoretical basis for developing innovative therapeutic strategies targeting the immune microenvironment.
Keywords: HSC; Macrophages; NK cells; Immune interactions; Liver fibrosis

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