The role of SH3BP2 in the pathogenesis of systemic lupus eryhematosus
| Project/Area Number |
18K08398
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井関 將典 川崎医科大学, 医学部, 講師 (30532353)
長洲 一 川崎医科大学, 医学部, 准教授 (40412176)
守田 吉孝 川崎医科大学, 医学部, 教授 (50346441)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | SH3BP2 / 全身性エリテマトーデス / Cherubism / Fas-lprマウス / 樹状細胞 / SLEモデルマウス / Faslprマウス / Imiquimod誘発SLEモデル / 自己抗体 / 自己反応性リンパ球 |
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| Outline of Final Research Achievements |
SH3BP2 (SH3 binding protein2) is an adaptor protein, which is widely expressed in immune cells and regulates intracellular signaling such as Syk. The role of SH3BP2 in autoimmune diseases is unclear. In this study, we investigated its effects on autoimmune phenomena and organ damage using a mouse model of systemic lupus erythematosus (SLE). The results showed that SH3BP2 deficiency reduced autoantibody production, increased abnormal T cells, and subsequently suppressed organ damage in the SLE mice. These findings suggest that SH3BP2 deficiency ameliorates SLE-like lesions through suppression of dendritic cell differentiation and activation.
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| Academic Significance and Societal Importance of the Research Achievements |
アダプラー蛋白質SH3BP2はもともと小児の顎骨破壊を特徴とするCherubismの原因遺伝子として同定された。SH3BP2のCherubism変異により、破骨細胞・マクロファージの活性化が生じCherubismの病態に関与することは過去に我々が報告したが、Cherubism以外の疾患におけるSH3BP2の役割は不明だった。本研究により、SH3BP2が自己免疫性疾患である全身性エリテマトーデス（SLE）の病態に関与することが分かった。本研究は、広く他の自己免疫疾患におけるSH3BP2の役割を解明する端緒になると考える。また、SH3BP2を標的とする新規治療戦略にもつながると考える。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Inhibition of Interleukin-6 Signaling Attenuates Aortitis, Left Ventricular Hypertrophy and Arthritis in Interleukin-1 Receptor Antagonist Deficient Mice.2020
Author(s)
Yoshiko Hada, Haruhito A. Uchida, Tomoyuki Mukai, Fumiaki Kojima, Masashi Yoshida, Hidemi Takeuchi, Yuki Kakio, Nozomu Otaka,Yoshitaka Morita, Jun Wada.
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Journal Title
Clin. Sci. (Lond).
Volume: 134
Issue: 20
Pages: 2771-2787
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The role of an adaptor protein SH3BP2 in the pathogenesis of systemic lupus erythematosus2020
Author(s)
Tomoyuki Mukai, Kyoko Kawahara, Masanori Iseki, Akiko Nagasu, Hajime Nagasu, Takahiko Akagi, Shoko Tsuji, Sumie Asano, Yasuyoshi Ueki, Katsuhiko Ishihara, Naoki Kashihara, Yoshitaka Morita
Organizer
第43回日本分子生物学会年会
Related Report
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[Presentation] SH3BP2 deficiency ameliorates murine systemic lupus erythematosus2020
Author(s)
Tomoyuki Mukai, Kyoko Kawahara, Masanori Iseki, Akiko Nagasu, Hajime Nagasu, Takahiko Akagi, Shoko Tsuji, Yasuyoshi Ueki, Katsuhiko Ishihara, Naoki Kashihara, Yoshitaka Morita
Organizer
The 22nd Asia Pacific League of Associations for Rheumatology (APLAR 2020)
Related Report
Int'l Joint Research
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[Presentation] 全身性エリテマトーデスモデルマウスにおけるアダプター蛋白SH3BP2 の自己免疫現象における役割の解明2020
Author(s)
河原恭子, 向井知之, 井関將典, 長洲晶子, 長洲一, 赤木貴彦, 辻尚子, 石原克彦, 柏原直樹, 植木靖好, 守田吉孝
Organizer
第41回日本炎症・再生医学会
Related Report
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