Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease
Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease
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DOI：
10.3390/immuno2010013
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发表时间：
2022-02
期刊：
影响因子：
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通讯作者：
N. Kaneko;M. Moriyama;T. Maehara;Hu Chen;Yuka Miyahara;Seiji Nakamura
中科院分区：
文献类型：
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作者：
N. Kaneko;M. Moriyama;T. Maehara;Hu Chen;Yuka Miyahara;Seiji Nakamura
本文综述了近年来对IgG4相关疾病（IgG4-RD）发病机制的研究进展，重点介绍了纤维化的发病机制。几项研究报道，在自身免疫性纤维化疾病（如IgG 4-RD、系统性硬化症和纤维化纵隔炎）中，由颗粒酶和穿孔素分泌促进的具有细胞毒性活性的CD4 + T细胞、细胞毒性CD4 + T细胞（CD4 + CTL）和疾病特异性活化B细胞浸润炎症组织并协同诱导组织纤维化。经历由CD4 + CTL和CD8 + CTL诱导的凋亡性细胞死亡的细胞积累，随后是巨噬细胞介导的清除，最后是由CD4 + CTL、活化的B细胞和M2巨噬细胞释放的细胞因子驱动的组织重塑，这可能有助于成纤维细胞的活化和胶原蛋白的产生。在IgG4-RD中，该过程可能涉及间充质来源的非免疫、非内皮细胞的凋亡和随后的组织重塑。总之，CD4 + CTL浸润受影响的组织，在那里它们可以与活化的B细胞、CD8 + CTL和M2巨噬细胞合作，通过分泌细胞毒性细胞因子来诱导细胞凋亡。这些免疫细胞还通过分泌IgG4-RD中的促纤维化分子来驱动纤维化。
This review summarizes recent progress in understanding the pathogenesis of IgG4-related disease (IgG4-RD), with a focus on fibrosis. Several studies reported that CD4+ T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4+ T cells (CD4+CTLs), and disease-specific activated B cells, infiltrated inflamed tissues and cooperated to induce tissue fibrosis in autoimmune fibrotic diseases such as IgG4-RD, systemic sclerosis, and fibrosing mediastinitis. An accumulation of cells undergoing apoptotic cell death induced by CD4+CTLs and CD8+CTLs followed by macrophage-mediated clearing and finally tissue remodeling driven by cytokines released by CD4+CTLs, activated B cells, and M2 macrophages may contribute to the activation of fibroblasts and collagen production. In IgG4-RD, this process likely involves the apoptosis of non-immune, non-endothelial cells of mesenchymal origin and subsequent tissue remodeling. In summary, CD4+CTLs infiltrate affected tissues where they may cooperate with activated B cells, CD8+CTLs, and M2 macrophages, to induce apoptosis by secreting cytotoxic cytokines. These immune cells also drive fibrosis by secreting pro-fibrotic molecules in IgG4-RD.