{"title":"巨噬细胞对以进行性纤维化为特征的系统性硬化症的干预:系统综述","authors":"","doi":"10.1016/j.autrev.2024.103637","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aim</h3><p>Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [<em>i.e.</em>, IL-4, IL-10, IL-13, and transforming growth factor (TGF-β)] involved in the fibrotic and anti-inflammatory process. A spectrum of macrophage activation state has been identified ranging from M1 to M2 phenotype, gene expression of phenotype markers, and functional aspects. This systematic review aims to analyze the importance of M2 macrophage polatization during the immune mediated process and the identification of specific pathways, cytokines, and chemokines involved in SSc pathogenesis. Moreover, this review provides an overview on the <em>in vitro</em> and <em>in vivo</em> studies aiming to test therapeutic strategies targeting M2 macrophages.</p></div><div><h3>Methods</h3><p>A systematic literature review was performed according to the preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA). The search encompassed the online medical databases PubMed and Embase up to the 30th of June 2024. Original research manuscripts (<em>in vitro</em> study, <em>in vivo</em> study), animal model and human cohort<del>,</del> were considered for the review. Exclusion criteria encompassed reviews, case reports, correspondences, and conference abstracts/posters. The eligible manuscripts main findings were critically analyzed, discussed, and summarized in the correspondent tables.</p></div><div><h3>Results</h3><p>Out of the 77 screened abstracts, 49 papers were deemed eligible. Following a critical analysis, they were categorized according to the primary (29 original articles) and secondary (20 original articles) research objectives of this systematic review. The data from the present systematic review suggest the pivotal role of M2 macrophages differentiation and activation together with the dysregulation of the immune system in the SSc pathogenesis. Strong correlations have been found between M2 macrophage presence and clinical manifestations in both murine and human tissue samples. Interestingly, the presence of M2 cell surface markers on peripheral blood monocytes has been highlighted, suggesting a potential biomarker role for this finding. Therapeutic effects reducing M2 macrophage activities have been observed and/or tested for existing and for new drugs, demonstrating potential efficacy in modulating the pro-fibrotic immune response for treatment of SSc.</p></div><div><h3>Conclusions</h3><p>The increased M2 macrophage activation in course of SSc seems to offer new insights on the self-amplifying inflammatory and fibrotic response by the immune system on such disease. Therefore, the revaluation of immunomodulatory and ongoing antifibrotic therapies, as well as novel therapeutical approaches in SSc that contribute to limit the M2 macrophage activation are matter of intense investigations.</p></div>","PeriodicalId":8664,"journal":{"name":"Autoimmunity reviews","volume":null,"pages":null},"PeriodicalIF":9.2000,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568997224001289/pdfft?md5=0a912fc4418a6e852931c6e499992eaf&pid=1-s2.0-S1568997224001289-main.pdf","citationCount":"0","resultStr":"{\"title\":\"The intervention of macrophages in progressive fibrosis characterizing systemic sclerosis: A systematic review\",\"authors\":\"\",\"doi\":\"10.1016/j.autrev.2024.103637\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aim</h3><p>Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [<em>i.e.</em>, IL-4, IL-10, IL-13, and transforming growth factor (TGF-β)] involved in the fibrotic and anti-inflammatory process. A spectrum of macrophage activation state has been identified ranging from M1 to M2 phenotype, gene expression of phenotype markers, and functional aspects. This systematic review aims to analyze the importance of M2 macrophage polatization during the immune mediated process and the identification of specific pathways, cytokines, and chemokines involved in SSc pathogenesis. Moreover, this review provides an overview on the <em>in vitro</em> and <em>in vivo</em> studies aiming to test therapeutic strategies targeting M2 macrophages.</p></div><div><h3>Methods</h3><p>A systematic literature review was performed according to the preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA). The search encompassed the online medical databases PubMed and Embase up to the 30th of June 2024. Original research manuscripts (<em>in vitro</em> study, <em>in vivo</em> study), animal model and human cohort<del>,</del> were considered for the review. Exclusion criteria encompassed reviews, case reports, correspondences, and conference abstracts/posters. The eligible manuscripts main findings were critically analyzed, discussed, and summarized in the correspondent tables.</p></div><div><h3>Results</h3><p>Out of the 77 screened abstracts, 49 papers were deemed eligible. Following a critical analysis, they were categorized according to the primary (29 original articles) and secondary (20 original articles) research objectives of this systematic review. The data from the present systematic review suggest the pivotal role of M2 macrophages differentiation and activation together with the dysregulation of the immune system in the SSc pathogenesis. Strong correlations have been found between M2 macrophage presence and clinical manifestations in both murine and human tissue samples. Interestingly, the presence of M2 cell surface markers on peripheral blood monocytes has been highlighted, suggesting a potential biomarker role for this finding. Therapeutic effects reducing M2 macrophage activities have been observed and/or tested for existing and for new drugs, demonstrating potential efficacy in modulating the pro-fibrotic immune response for treatment of SSc.</p></div><div><h3>Conclusions</h3><p>The increased M2 macrophage activation in course of SSc seems to offer new insights on the self-amplifying inflammatory and fibrotic response by the immune system on such disease. Therefore, the revaluation of immunomodulatory and ongoing antifibrotic therapies, as well as novel therapeutical approaches in SSc that contribute to limit the M2 macrophage activation are matter of intense investigations.</p></div>\",\"PeriodicalId\":8664,\"journal\":{\"name\":\"Autoimmunity reviews\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.2000,\"publicationDate\":\"2024-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1568997224001289/pdfft?md5=0a912fc4418a6e852931c6e499992eaf&pid=1-s2.0-S1568997224001289-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autoimmunity reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1568997224001289\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568997224001289","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
The intervention of macrophages in progressive fibrosis characterizing systemic sclerosis: A systematic review
Background and aim
Systemic sclerosis (SSc) is an immune mediated connective tissue disease characterized by microvascular dysfunction, aberrant immune response, and progressive fibrosis. Although the immuno-pathophysiological mechanisms underlying SSc are not fully clarified, they are often associated with a dysfunctional macrophage activation toward an alternative (M2) phenotype induced by cytokines [i.e., IL-4, IL-10, IL-13, and transforming growth factor (TGF-β)] involved in the fibrotic and anti-inflammatory process. A spectrum of macrophage activation state has been identified ranging from M1 to M2 phenotype, gene expression of phenotype markers, and functional aspects. This systematic review aims to analyze the importance of M2 macrophage polatization during the immune mediated process and the identification of specific pathways, cytokines, and chemokines involved in SSc pathogenesis. Moreover, this review provides an overview on the in vitro and in vivo studies aiming to test therapeutic strategies targeting M2 macrophages.
Methods
A systematic literature review was performed according to the preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA). The search encompassed the online medical databases PubMed and Embase up to the 30th of June 2024. Original research manuscripts (in vitro study, in vivo study), animal model and human cohort, were considered for the review. Exclusion criteria encompassed reviews, case reports, correspondences, and conference abstracts/posters. The eligible manuscripts main findings were critically analyzed, discussed, and summarized in the correspondent tables.
Results
Out of the 77 screened abstracts, 49 papers were deemed eligible. Following a critical analysis, they were categorized according to the primary (29 original articles) and secondary (20 original articles) research objectives of this systematic review. The data from the present systematic review suggest the pivotal role of M2 macrophages differentiation and activation together with the dysregulation of the immune system in the SSc pathogenesis. Strong correlations have been found between M2 macrophage presence and clinical manifestations in both murine and human tissue samples. Interestingly, the presence of M2 cell surface markers on peripheral blood monocytes has been highlighted, suggesting a potential biomarker role for this finding. Therapeutic effects reducing M2 macrophage activities have been observed and/or tested for existing and for new drugs, demonstrating potential efficacy in modulating the pro-fibrotic immune response for treatment of SSc.
Conclusions
The increased M2 macrophage activation in course of SSc seems to offer new insights on the self-amplifying inflammatory and fibrotic response by the immune system on such disease. Therefore, the revaluation of immunomodulatory and ongoing antifibrotic therapies, as well as novel therapeutical approaches in SSc that contribute to limit the M2 macrophage activation are matter of intense investigations.
期刊介绍:
Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers.
The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences.
In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations.
Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.