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      Role of Immune Cells in Biliary Repair

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          Abstract

          The biliary system is comprised of cholangiocytes and plays an important role in maintaining liver function. Under normal conditions, cholangiocytes remain in the stationary phase and maintain a very low turnover rate. However, the robust biliary repair is initiated in disease conditions, and different repair mechanisms can be activated depending on the pathological changes. During biliary disease, immune cells including monocytes, lymphocytes, neutrophils, and mast cells are recruited to the liver. The cellular interactions between cholangiocytes and these recruited immune cells as well as hepatic resident immune cells, including Kupffer cells, determine disease outcomes. However, the role of immune cells in the initiation, regulation, and suspension of biliary repair remains elusive. The cellular processes of cholangiocyte proliferation, progenitor cell differentiation, and hepatocyte-cholangiocyte transdifferentiation during biliary diseases are reviewed to manifest the underlying mechanism of biliary repair. Furthermore, the potential role of immune cells in crucial biliary repair mechanisms is highlighted. The mechanisms of biliary repair in immune-mediated cholangiopathies, inherited cholangiopathies, obstructive cholangiopathies, and cholangiocarcinoma are also summarized. Additionally, novel techniques that could clarify the underlying mechanisms of biliary repair are displayed. Collectively, this review aims to deepen the understanding of the mechanisms of biliary repair and contributes potential novel therapeutic methods for treating biliary diseases.

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          Most cited references209

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          Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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            Macrophage Polarization.

            Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and the normal tissue environment. Three broad pathways control polarization: epigenetic and cell survival pathways that prolong or shorten macrophage development and viability, the tissue microenvironment, and extrinsic factors, such as microbial products and cytokines released in inflammation. A plethora of advances have provided a framework for rationally purifying, describing, and manipulating macrophage polarization. Here, I assess the current state of knowledge about macrophage polarization and enumerate the major questions about how activated macrophages regulate the physiology of normal and damaged tissues.
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              Mechanisms of hepatic stellate cell activation

              Activation of hepatic stellate cells (HSCs) in liver injury is the primary driver of hepatic fibrosis. In this Review, Tsuchida and Friedman detail the varied intracellular and extracellular signalling pathways leading to HSC activation, as well as the role of HSCs in liver fibrosis resolution and as therapeutic targets.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 March 2022
                2022
                : 13
                : 866040
                Affiliations
                [1] 1 Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China
                [2] 2 Department of Gastroenterology, West China Hospital, Sichuan University , Chengdu, China
                Author notes

                Edited by: Niloufar Safinia, King’s College London, United Kingdom

                Reviewed by: James Ahodantin, University of Maryland, Baltimore, United States; Matthias Bartneck, University Hospital RWTH Aachen, Germany

                †These authors have contributed equally to this work

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.866040
                9005827
                35432349
                03c84982-fa3f-4b06-81e3-9387f61722c5
                Copyright © 2022 Lan, Qian, Tang and Gao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 January 2022
                : 08 March 2022
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 209, Pages: 18, Words: 8818
                Funding
                Funded by: National Science Foundation , doi 10.13039/100000001;
                Categories
                Immunology
                Review

                Immunology
                cholangiopathy,biliary repair,liver progenitor cell,macrophage,hepatocyte-cholangiocyte transdifferentiation,immune cells

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