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

IF 9.2 1区 医学 Q1 IMMUNOLOGY Autoimmunity reviews Pub Date : 2024-09-08 DOI:10.1016/j.autrev.2024.103637
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引用次数: 0

摘要

背景和目的系统性硬化症(SSc)是一种免疫介导的结缔组织疾病,其特点是微血管功能障碍、免疫反应异常和进行性纤维化。尽管系统性硬化症的免疫病理生理机制尚未完全阐明,但它们通常与巨噬细胞功能失调活化有关,在参与纤维化和抗炎过程的细胞因子[即 IL-4、IL-10、IL-13 和转化生长因子 (TGF-β)]的诱导下,巨噬细胞向替代 (M2) 表型活化。巨噬细胞活化状态的范围已从 M1 到 M2 表型、表型标志物的基因表达和功能方面确定下来。本系统综述旨在分析 M2 巨噬细胞在免疫介导过程中极化的重要性,并确定参与 SSc 发病机制的特定途径、细胞因子和趋化因子。此外,本综述还概述了旨在测试针对 M2 巨噬细胞的治疗策略的体外和体内研究。方法根据系统综述和荟萃分析首选报告项目(PRISMA)进行了系统性文献综述。检索范围包括截至 2024 年 6 月 30 日的在线医学数据库 PubMed 和 Embase。原始研究手稿(体外研究、体内研究)、动物模型和人类队列均在审查之列。排除标准包括综述、病例报告、通信和会议摘要/海报。对符合条件的稿件的主要研究结果进行了批判性分析、讨论,并在相应的表格中进行了总结。经过批判性分析后,这些论文按照本系统综述的主要研究目标(29 篇原创文章)和次要研究目标(20 篇原创文章)进行了分类。本系统综述的数据表明,M2 巨噬细胞的分化和活化以及免疫系统失调在 SSc 发病机制中起着关键作用。在小鼠和人体组织样本中发现,M2 巨噬细胞的存在与临床表现之间存在很强的相关性。有趣的是,外周血单核细胞上存在 M2 细胞表面标记物,这表明这一发现具有潜在的生物标记作用。通过观察和/或测试现有药物和新药降低 M2 巨噬细胞活性的治疗效果,证明了调节促纤维化免疫反应以治疗 SSc 的潜在疗效。因此,重新评估免疫调节疗法和正在进行的抗纤维化疗法,以及有助于限制 M2 巨噬细胞活化的 SSc 新型治疗方法,都是需要深入研究的问题。
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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.

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来源期刊
Autoimmunity reviews
Autoimmunity reviews 医学-免疫学
CiteScore
24.70
自引率
4.40%
发文量
164
审稿时长
21 days
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.
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