Abstract
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.
Highlights
Introduction and Clinical FeaturesAutoimmune fibrotic diseases including systemic sclerosis (SSc), lupus nephritis, fibrosing mediastinitis, and IgG4-related disease (IgG4-RD) are being studied by many rheumatologists and immunologists because of their variety of symptoms and difficulty in treatment, especially in relapse cases
A number of reviews have described the clinical features of IgG4-RD, a multi-organ inflammatory condition characterized by elevated serum IgG4 levels and lymphoplasmacytic infiltrate composed of a large population of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis [5,6,7,8]
II moland SLAMF7 are expanded in high numbers and undergo somatic hypermutation in IgG4ecules to CD4+ T cells, which likely contributes to the pathogenesis of IgG4-RD [36]
Summary
Autoimmune fibrotic diseases including systemic sclerosis (SSc), lupus nephritis, fibrosing mediastinitis, and IgG4-related disease (IgG4-RD) are being studied by many rheumatologists and immunologists because of their variety of symptoms and difficulty in treatment, especially in relapse cases. Killing depending on the tissue microenvironment cell depletion therapy by of plasmablasts and CD4 CTLs in the blood and tissues, and tissue fibrosis by attenuating rituximab induced a period of remission and swift clinical improvement in patients with the secretory phenotype of myofibroblasts [26,34,35]. These clinical observations followIgG4-RD [28]. Circulating plasmablasts and activated B cells that express high levels of surface
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