Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis

Minjie Wan; Jiawen Han; Lili Ding; Feng Hu; Pujun Gao

doi:10.3389/fmed.2021.604894

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis

Front Med (Lausanne). 2021 Apr 1:8:604894. doi: 10.3389/fmed.2021.604894. eCollection 2021.

Authors

Minjie Wan^{1

2}, Jiawen Han², Lili Ding^{2

3}, Feng Hu⁴, Pujun Gao¹

Affiliations

¹ Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, China.
² Central Laboratory, The First Hospital of Jilin University, Jilin University, Changchun, China.
³ Intensive Care Unit, The First Hospital of Jilin University, Jilin University, Changchun, China.
⁴ Department of Hepatology and Gastroenterology, The Second Part of First Hospital, Jilin University, Changchun, China.

Abstract

Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.

Keywords: T helper cells; hepatic stellate cells; innate lymphoid cells; liver fibrosis; mucosa-associated invariant T cells; regulatory T cells.

Publication types

Review