| Project/Area Number |
18K09323
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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 56050:Otorhinolaryngology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IgG4関連疾患 / 細胞傷害性Tfh細胞 / Tfh細胞 / IgG4関連涙腺・唾液腺炎 / memory B 細胞 / Tph細胞 |
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| Outline of Final Research Achievements |
We analyzed CD4+CD8+ Tfh cells and B cell subsets from submandibular glands (SMGs) of patients with IgG4-RD by flow cytometry. The percentage of CD4+CD8+ Tfh cells in IgG4-RD SMGs was increased compared with that in tonsils and was negatively correlated with the percentage of memory B cells in IgG4-RD SMGs. In a coculture experiment with CD4+CD8+ Tfh cells and memory B cells from IgG4-RD SMGs, the amount of IgG produced by memory B cells in the culture supernatant was reduced. In vitro experiments also revealed that CD4+CD8+ Tfh cells have a functional capacity for production of a large amount of granzyme. The results suggest that the number of CD4+CD8+ Tfh cells was increased under the condition of chronic inflammation and that the cells exerted cytotoxity to memory B cells. Therefore, CD4+CD8+ Tfh cells inhibit the production of IgG from memory B cells and regulate immune responses in lesions of IgG4-RD.
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| Academic Significance and Societal Importance of the Research Achievements |
現在のところIgG4-RDの病因は不明である。今回我々はIgG4-RDの病変部位に存在するTfh細胞を直接解析することにより、細胞傷害性Tfh細胞という新しい細胞群を発見することができた。細胞傷害性Tfh細胞の機能的役割の解明はIgG4-RDにとどまらず、その他の難治性慢性炎症性疾患の病態の新たな理解や治療法の臨床応用に向けて、これまでにない展開がもたらされることが期待される。細胞傷害性Tfh細胞を標的にするIgG4-RDの新規治療法が実用化されれば、従来のグルココルチコイドに代わる副作用の少ない治療が可能となり、多くのIgG4-RDの患者がその恩恵を受けることになると確信している。
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