| Project/Area Number |
17K11663
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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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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Tokyo Dental College (2019)
Tokyo Medical and Dental University (2017-2018) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | VISTA / 抑制性共刺激分子 / 歯周病 / アレルギー性気道炎症 / マウスモデル / 共刺激分子 / LPS / 歯周炎 / マクロファージ / PD-1H / 免疫チェックポイント |
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| Outline of Final Research Achievements |
VISTA is a novel immune checkpoint receptor and ligand that regulates T-cell activation. We investigated the functional involvement of VISTA in periodontitis using LPS-induced periodontitis model. Treatment with an anti-VISTA monoclonal antibody (mAb) enhanced the LPS-induced TNFa and IL-1b expression in gingiva and alveolar bone resorption. We also investigated the functional involvement of VISTA in Th2 cell-mediated immune responses using an OVA-induced allergic asthma model. Treatment with the anti-VISTA mAb during allergen challenge, but not sensitization, significantly augmented AHR and BAL fluid eosinophilia. This treatment also increased the production of IL-5 and IL-13 in BAL fluid and the expression of IL-13 by CD4+ T cells in draining lymph nodes. These results suggest that VISTA is involved in the regulation of both LPS-induced immune responses and antigen specific Th2 cell generation, and regulates periodontitis pathology and asthmatic responses, respectively.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、これまでに明らかにされていなかった歯周病病態形成過程の自然免疫応答やアレルギー応答に関与するTh2型免疫応答における共刺激分子VISTAの機能を明らかにすることができた。歯周病病態形成過程においてVISTAは炎症局所の急性炎症とともに慢性炎症によって誘導されると考えられる歯槽骨吸収を抑制的に制御していると考えられた。またTh2型応答であるアレルギー性気道炎症においてもVISTAはその病態を抑制的に制御していると考えられた。VISTAがこれら疾患の病態誘導を抑制的に制御していることから、VISTAを新たな標的分子としたこれら疾患に対する新規治療法の開発が期待される。
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