Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells
Abstract Purpose This research investigates the role of inhibitor of differentiation 2 (Id2) in the synthesis of pro‐inflammatory cytokines, specifically interferon‐γ (IFN‐γ) and interleukin‐17 (IL‐17), by various subsets of T cells, and its pathogenic role in rheumatoid arthritis (RA). Methods Flow...
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Wiley
2025-03-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70242 |
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| author | Haoyang Sun Jinlin Miao Kui Zhang Peiyan Zhang Haomiao Shen Jiawei Wang Bei Zhang Junfeng Jia Zhaohui Zheng Ping Zhu |
| author_facet | Haoyang Sun Jinlin Miao Kui Zhang Peiyan Zhang Haomiao Shen Jiawei Wang Bei Zhang Junfeng Jia Zhaohui Zheng Ping Zhu |
| author_sort | Haoyang Sun |
| collection | DOAJ |
| description | Abstract Purpose This research investigates the role of inhibitor of differentiation 2 (Id2) in the synthesis of pro‐inflammatory cytokines, specifically interferon‐γ (IFN‐γ) and interleukin‐17 (IL‐17), by various subsets of T cells, and its pathogenic role in rheumatoid arthritis (RA). Methods Flow cytometry was employed to assess T‐cell activation and Id2 expression in 72 RA patients and 23 healthy controls. In vitro, peripheral blood mononuclear cells were treated with either an Id2 inhibitor or a T‐cell co‐stimulation inhibitor. An in vivo collagen‐induced arthritis (CIA) model was established using T‐cell‐specific Id2 knockout mice. Additionally, follow‐up observations were conducted among treated RA patients. Results T‐cell activation levels in RA synovial fluid were significantly elevated. A positive correlation was found between increased IFN‐γ and Id2 expression. In vitro, antagonising Id2 reduced IFN‐γ production after T‐cell activation. T‐cell‐specific Id2 knockout mice exhibited a diminished occurrence and severity of CIA, along with a significant decrease in IFN‐γ expression. Clinical monitoring indicated that Id2‐induced circulating T‐cell IFN‐γ expression significantly decreased following treatment with the T‐cell activation inhibitor abatacept. Conclusion The data suggest that high Id2 expression is a critical regulator of pro‐inflammatory cytokine upregulation, particularly IFN‐γ, by hyperactivated T cells in RA, potentially exacerbating the disease. Inhibiting Id2 expression or function may offer new therapeutic approaches for RA joint inflammation. Key points Pro‐inflammatory cytokines are significantly upregulated in the synovial fluid T cells in rheumatoid arthritis patients. The expression of pro‐inflammatory cytokine interferon‐γ (IFN‐γ) positively correlates with the high expression of inhibitor of differentiation 2 (Id2). The inhibition or ablation of Id2 can effectively suppress IFN‐γ production and the onset and progression of arthritis. |
| format | Article |
| id | doaj-art-2b990e5e64154b1ba0a31cb53076c879 |
| institution | OA Journals |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj-art-2b990e5e64154b1ba0a31cb53076c8792025-08-20T02:32:12ZengWileyClinical and Translational Medicine2001-13262025-03-01153n/an/a10.1002/ctm2.70242Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cellsHaoyang Sun0Jinlin Miao1Kui Zhang2Peiyan Zhang3Haomiao Shen4Jiawei Wang5Bei Zhang6Junfeng Jia7Zhaohui Zheng8Ping Zhu9Department of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaDepartment of Clinical Immunology Xijing Hospital, Fourth Military Medical University Xi'an ChinaAbstract Purpose This research investigates the role of inhibitor of differentiation 2 (Id2) in the synthesis of pro‐inflammatory cytokines, specifically interferon‐γ (IFN‐γ) and interleukin‐17 (IL‐17), by various subsets of T cells, and its pathogenic role in rheumatoid arthritis (RA). Methods Flow cytometry was employed to assess T‐cell activation and Id2 expression in 72 RA patients and 23 healthy controls. In vitro, peripheral blood mononuclear cells were treated with either an Id2 inhibitor or a T‐cell co‐stimulation inhibitor. An in vivo collagen‐induced arthritis (CIA) model was established using T‐cell‐specific Id2 knockout mice. Additionally, follow‐up observations were conducted among treated RA patients. Results T‐cell activation levels in RA synovial fluid were significantly elevated. A positive correlation was found between increased IFN‐γ and Id2 expression. In vitro, antagonising Id2 reduced IFN‐γ production after T‐cell activation. T‐cell‐specific Id2 knockout mice exhibited a diminished occurrence and severity of CIA, along with a significant decrease in IFN‐γ expression. Clinical monitoring indicated that Id2‐induced circulating T‐cell IFN‐γ expression significantly decreased following treatment with the T‐cell activation inhibitor abatacept. Conclusion The data suggest that high Id2 expression is a critical regulator of pro‐inflammatory cytokine upregulation, particularly IFN‐γ, by hyperactivated T cells in RA, potentially exacerbating the disease. Inhibiting Id2 expression or function may offer new therapeutic approaches for RA joint inflammation. Key points Pro‐inflammatory cytokines are significantly upregulated in the synovial fluid T cells in rheumatoid arthritis patients. The expression of pro‐inflammatory cytokine interferon‐γ (IFN‐γ) positively correlates with the high expression of inhibitor of differentiation 2 (Id2). The inhibition or ablation of Id2 can effectively suppress IFN‐γ production and the onset and progression of arthritis.https://doi.org/10.1002/ctm2.70242abataceptIFN‐γinhibitor of differentiation 2rheumatoid arthritisT cell |
| spellingShingle | Haoyang Sun Jinlin Miao Kui Zhang Peiyan Zhang Haomiao Shen Jiawei Wang Bei Zhang Junfeng Jia Zhaohui Zheng Ping Zhu Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells Clinical and Translational Medicine abatacept IFN‐γ inhibitor of differentiation 2 rheumatoid arthritis T cell |
| title | Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells |
| title_full | Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells |
| title_fullStr | Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells |
| title_full_unstemmed | Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells |
| title_short | Id2 exacerbates the development of rheumatoid arthritis by increasing IFN‐γ production in CD4+ T cells |
| title_sort | id2 exacerbates the development of rheumatoid arthritis by increasing ifn γ production in cd4 t cells |
| topic | abatacept IFN‐γ inhibitor of differentiation 2 rheumatoid arthritis T cell |
| url | https://doi.org/10.1002/ctm2.70242 |
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