Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

Nana Zhang; Huimin Yao; Zhixuan Zhang; Zhuoqun Li; Xue Chen; Yan Zhao; Ran Ju; Jiayi He; Heli Pan; Xiaoli Liu; Yi Lv

doi:10.3389/fimmu.2023.1131588

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

Front Immunol. 2023 Feb 16:14:1131588. doi: 10.3389/fimmu.2023.1131588. eCollection 2023.

Authors

Nana Zhang^{1

2

3}, Huimin Yao^{1

2

3}, Zhixuan Zhang^{1

2

3}, Zhuoqun Li^{2

3

4}, Xue Chen^{2

3}, Yan Zhao^{1

2

3}, Ran Ju^{1

2

3}, Jiayi He^{1

2

3}, Heli Pan^{1

2

3}, Xiaoli Liu^{1

2

3}, Yi Lv^{1

2

3

4}

Affiliations

¹ Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases' reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.

Keywords: chronic liver diseases; hepatic fibrosis; hepatic immune microenvironment; hepatic stellate cells (HSCs); immune cells.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cytokines
Humans
Liver Cirrhosis*
Liver Neoplasms*
Retrospective Studies
Tumor Microenvironment

Substances

Cytokines

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 82202297, Grant No. 81900573), and the Natural Science Basic Research Program of Shaanxi Province (Grant No. 2022JQ-914).