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      Immune microenvironment changes of liver cirrhosis: emerging role of mesenchymal stromal cells

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          Abstract

          Cirrhosis is a progressive and diffuse liver disease characterized by liver tissue fibrosis and impaired liver function. This condition is brought about by several factors, including chronic hepatitis, hepatic steatosis, alcohol abuse, and other immunological injuries. The pathogenesis of liver cirrhosis is a complex process that involves the interaction of various immune cells and cytokines, which work together to create the hepatic homeostasis imbalance in the liver. Some studies have indicated that alterations in the immune microenvironment of liver cirrhosis are closely linked to the development and prognosis of the disease. The noteworthy function of mesenchymal stem cells and their paracrine secretion lies in their ability to promote the production of cytokines, which in turn enhance the self-repairing capabilities of tissues. The objective of this review is to provide a summary of the alterations in liver homeostasis and to discuss intercellular communication within the organ. Recent research on MSCs is yielding a blueprint for cell typing and biomarker immunoregulation. Hopefully, as MSCs researches continue to progress, novel therapeutic approaches will emerge to address cirrhosis.

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          Most cited references210

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          Pattern recognition receptors and inflammation.

          Osamu Takeuchi, Shizuo Akira (2010)
          Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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            Macrophage plasticity and polarization: in vivo veritas.

            Antonio Sica, Alberto Mantovani (2012)
            Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
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              Burden of liver diseases in the world

              Sumeet K Asrani, Harshad Devarbhavi, John Eaton … (2019)
              Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Immunol
                Journal ID (iso-abbrev): Front Immunol
                Journal ID (publisher-id): Front. Immunol.
                Title: Frontiers in Immunology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-3224
                Publication date (Electronic): 19 July 2023
                Publication date Collection: 2023
                Volume: 14
                Electronic Location Identifier: 1204524
                Affiliations
                [1] 1 National Center for Liver Cancer, Third Affiliated Hospital of Naval Medical University , Shanghai, China
                [2] 2 International Cooperation Laboratory on Signal Transduction, Third Affiliated Hospital of Naval Medical University (Second Military Medical University) , Shanghai, China
                [3] 3 Department of Breast and Thyroid Surgery, Changhai Hospital, Naval Military Medical University , Shanghai, China
                [4] 4 Department of Laboratory Diagnosis, Third Affiliated Hospital of Naval Medical University (Second Military Medical University) , Shanghai, China
                Author notes

                Edited by: Yongzhan Nie, Fourth Military Medical University, China

                Reviewed by: Debanjali Dasgupta, Mayo Clinic, United States; Theodore Cory, University of Tennessee Health Science Center (UTHSC), United States

                *Correspondence: Wen Wen, wenwen_smmu@ 123456163.com

                †These authors contributed equally to this work and share first authorship

                Article
                DOI: 10.3389/fimmu.2023.1204524
                PMC ID: 10395751
                SO-VID: ed364522-4415-4536-a8f2-ee8c97ecf945
                Copyright © Copyright © 2023 Yi, Yang, Wu, Wang, Cao and Wen
                License:

                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
                Date received : 12 April 2023
                Date accepted : 21 June 2023
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 211, Pages: 15, Words: 7181
                Funding
                Funded by: Shanghai Municipal Health Commission , doi 10.13039/100017950;
                This review was supported by the National Natural Science Foundation of China (82072600). The plan of the Shanghai Municipal Health Commission (2022XD036) also provided funding to conduct this project.
                Categories
                Subject: Immunology
                Subject: Review
                Custom metadata
                section-in-acceptance Cytokines and Soluble Mediators in Immunity

                ScienceOpen disciplines: Immunology
                Keywords: liver cirrhosis,liver immune microenvironment,mesenchymal stromal cells,nonalcoholic fatty lives disease,autoimmune liver disease,chronic liver disease,therapy
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: liver cirrhosis, liver immune microenvironment, mesenchymal stromal cells, nonalcoholic fatty lives disease, autoimmune liver disease, chronic liver disease, therapy

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