Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome
Abstract Background Behçet’s syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationsh...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02867-x |
| _version_ | 1811215725645266944 |
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| author | Mai Okubo Shuji Sumitomo Yumi Tsuchida Yasuo Nagafuchi Yusuke Takeshima Haruyuki Yanaoka Harumi Shirai Satomi Kobayashi Yusuke Sugimori Junko Maeda Hiroaki Hatano Yukiko Iwasaki Hirofumi Shoda Tomohisa Okamura Kazuhiko Yamamoto Mineto Ota Keishi Fujio |
| author_facet | Mai Okubo Shuji Sumitomo Yumi Tsuchida Yasuo Nagafuchi Yusuke Takeshima Haruyuki Yanaoka Harumi Shirai Satomi Kobayashi Yusuke Sugimori Junko Maeda Hiroaki Hatano Yukiko Iwasaki Hirofumi Shoda Tomohisa Okamura Kazuhiko Yamamoto Mineto Ota Keishi Fujio |
| author_sort | Mai Okubo |
| collection | DOAJ |
| description | Abstract Background Behçet’s syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors. Methods ImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes. Results The frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8+ T cells with HLA-B51; therefore, IL-17-producing CD8+ T cells, Tc17 cells, may play a critical role in BS. Conclusions Various cells including CD4+ T cells, CD8+ T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS. |
| first_indexed | 2024-04-12T06:27:08Z |
| format | Article |
| id | doaj.art-98e13650dc0e400799ee89bcc981c0ed |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-12T06:27:08Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-98e13650dc0e400799ee89bcc981c0ed2022-12-22T03:44:06ZengBMCArthritis Research & Therapy1478-63622022-08-0124111210.1186/s13075-022-02867-xTranscriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndromeMai Okubo0Shuji Sumitomo1Yumi Tsuchida2Yasuo Nagafuchi3Yusuke Takeshima4Haruyuki Yanaoka5Harumi Shirai6Satomi Kobayashi7Yusuke Sugimori8Junko Maeda9Hiroaki Hatano10Yukiko Iwasaki11Hirofumi Shoda12Tomohisa Okamura13Kazuhiko Yamamoto14Mineto Ota15Keishi Fujio16Department of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoDepartment of Allergy and Rheumatology, Graduate School of Medicine, The University of TokyoAbstract Background Behçet’s syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors. Methods ImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes. Results The frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8+ T cells with HLA-B51; therefore, IL-17-producing CD8+ T cells, Tc17 cells, may play a critical role in BS. Conclusions Various cells including CD4+ T cells, CD8+ T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS.https://doi.org/10.1186/s13075-022-02867-xBehçet’s syndromeTranscriptomeInterleukin-17YBX3Antigen-presenting cells |
| spellingShingle | Mai Okubo Shuji Sumitomo Yumi Tsuchida Yasuo Nagafuchi Yusuke Takeshima Haruyuki Yanaoka Harumi Shirai Satomi Kobayashi Yusuke Sugimori Junko Maeda Hiroaki Hatano Yukiko Iwasaki Hirofumi Shoda Tomohisa Okamura Kazuhiko Yamamoto Mineto Ota Keishi Fujio Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome Arthritis Research & Therapy Behçet’s syndrome Transcriptome Interleukin-17 YBX3 Antigen-presenting cells |
| title | Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome |
| title_full | Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome |
| title_fullStr | Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome |
| title_full_unstemmed | Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome |
| title_short | Transcriptome analysis of immune cells from Behçet’s syndrome patients: the importance of IL-17-producing cells and antigen-presenting cells in the pathogenesis of Behçet’s syndrome |
| title_sort | transcriptome analysis of immune cells from behcet s syndrome patients the importance of il 17 producing cells and antigen presenting cells in the pathogenesis of behcet s syndrome |
| topic | Behçet’s syndrome Transcriptome Interleukin-17 YBX3 Antigen-presenting cells |
| url | https://doi.org/10.1186/s13075-022-02867-x |
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