Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease
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<sup>+</sup> T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4<sup>...
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MDPI AG
2022-02-01
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| Series: | Immuno |
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| Online Access: | https://www.mdpi.com/2673-5601/2/1/13 |
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| author | Naoki Kaneko Masafumi Moriyama Takashi Maehara Hu Chen Yuka Miyahara Seiji Nakamura |
| author_facet | Naoki Kaneko Masafumi Moriyama Takashi Maehara Hu Chen Yuka Miyahara Seiji Nakamura |
| author_sort | Naoki Kaneko |
| collection | DOAJ |
| description | 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<sup>+</sup> T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4<sup>+</sup> T cells (CD4<sup>+</sup>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<sup>+</sup>CTLs and CD8<sup>+</sup>CTLs followed by macrophage-mediated clearing and finally tissue remodeling driven by cytokines released by CD4<sup>+</sup>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<sup>+</sup>CTLs infiltrate affected tissues where they may cooperate with activated B cells, CD8<sup>+</sup>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. |
| first_indexed | 2024-03-09T19:40:56Z |
| format | Article |
| id | doaj.art-ea114c33fcdb4f2ba296ee265d1f4b09 |
| institution | Directory Open Access Journal |
| issn | 2673-5601 |
| language | English |
| last_indexed | 2024-03-09T19:40:56Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Immuno |
| spelling | doaj.art-ea114c33fcdb4f2ba296ee265d1f4b092023-11-24T01:40:25ZengMDPI AGImmuno2673-56012022-02-012117018410.3390/immuno2010013Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related DiseaseNaoki Kaneko0Masafumi Moriyama1Takashi Maehara2Hu Chen3Yuka Miyahara4Seiji Nakamura5Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanSection of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanThis review summarizes recent progress in understanding the pathogenesis of IgG4-related disease (IgG4-RD), with a focus on fibrosis. Several studies reported that CD4<sup>+</sup> T cells with cytotoxic activity promoted by the secretion of granzyme and perforin, cytotoxic CD4<sup>+</sup> T cells (CD4<sup>+</sup>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<sup>+</sup>CTLs and CD8<sup>+</sup>CTLs followed by macrophage-mediated clearing and finally tissue remodeling driven by cytokines released by CD4<sup>+</sup>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<sup>+</sup>CTLs infiltrate affected tissues where they may cooperate with activated B cells, CD8<sup>+</sup>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.https://www.mdpi.com/2673-5601/2/1/13cytotoxic CD4<sup>+</sup> T cellsactivated B cellsmacrophagesfibrosisIgG4-related disease |
| spellingShingle | Naoki Kaneko Masafumi Moriyama Takashi Maehara Hu Chen Yuka Miyahara Seiji Nakamura Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease Immuno cytotoxic CD4<sup>+</sup> T cells activated B cells macrophages fibrosis IgG4-related disease |
| title | Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease |
| title_full | Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease |
| title_fullStr | Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease |
| title_full_unstemmed | Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease |
| title_short | Orchestration of Immune Cells Contributes to Fibrosis in IgG4-Related Disease |
| title_sort | orchestration of immune cells contributes to fibrosis in igg4 related disease |
| topic | cytotoxic CD4<sup>+</sup> T cells activated B cells macrophages fibrosis IgG4-related disease |
| url | https://www.mdpi.com/2673-5601/2/1/13 |
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