Interorgan communication with the liver: novel mechanisms and therapeutic targets

Jiulu Zhao; Xi Zhang; Yuan Li; Jizhang Yu; Zhang Chen; Yuqing Niu; Shuan Ran; Song Wang; Weicong Ye; Zilong Luo; Xiaohan Li; Yanglin Hao; Junjie Zong; Chengkun Xia; Jiahong Xia; Jie Wu

doi:10.3389/fimmu.2023.1314123

Interorgan communication with the liver: novel mechanisms and therapeutic targets

Front Immunol. 2023 Dec 12:14:1314123. doi: 10.3389/fimmu.2023.1314123. eCollection 2023.

Authors

Jiulu Zhao^#^{1

2}, Xi Zhang^#^{1

2}, Yuan Li^#^{1

2}, Jizhang Yu^{1

2}, Zhang Chen^{1

2}, Yuqing Niu^{1

2}, Shuan Ran^{1

2}, Song Wang^{1

2}, Weicong Ye^{1

2}, Zilong Luo^{1

2}, Xiaohan Li^{1

2}, Yanglin Hao^{1

2}, Junjie Zong^{1

2}, Chengkun Xia³, Jiahong Xia^{1

2

4}, Jie Wu^{1

2

4}

Affiliations

¹ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Key Laboratory of Organ Transplantation, Ministry of Education, National Health Commission Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.

^# Contributed equally.

Abstract

The liver is a multifunctional organ that plays crucial roles in numerous physiological processes, such as production of bile and proteins for blood plasma, regulation of blood levels of amino acids, processing of hemoglobin, clearance of metabolic waste, maintenance of glucose, etc. Therefore, the liver is essential for the homeostasis of organisms. With the development of research on the liver, there is growing concern about its effect on immune cells of innate and adaptive immunity. For example, the liver regulates the proliferation, differentiation, and effector functions of immune cells through various secreted proteins (also known as "hepatokines"). As a result, the liver is identified as an important regulator of the immune system. Furthermore, many diseases resulting from immune disorders are thought to be related to the dysfunction of the liver, including systemic lupus erythematosus, multiple sclerosis, and heart failure. Thus, the liver plays a role in remote immune regulation and is intricately linked with systemic immunity. This review provides a comprehensive overview of the liver remote regulation of the body's innate and adaptive immunity regarding to main areas: immune-related molecules secreted by the liver and the liver-resident cells. Additionally, we assessed the influence of the liver on various facets of systemic immune-related diseases, offering insights into the clinical application of target therapies for liver immune regulation, as well as future developmental trends.

Keywords: hepatokine; immune cells; immune homeostasis; immune related diseases; immunity; liver; organ communication.

Publication types

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

MeSH terms

Adaptive Immunity
Humans
Immunity, Innate
Liver
Lupus Erythematosus, Systemic* / therapy
Multiple Sclerosis*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The figures in this review were created with BioRender.com. This review work was supported by the National Natural Science Foundation of China (82071803, 82271811, 81730015, 82241217) and Fundamental Research Funds for the Central Universities (2021GCRC037, YCJJ20230232 to SR).