| Project/Area Number |
18H02632
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-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 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | 濾胞ヘルパーT細胞 / 記憶B細胞 / DP-Tfh細胞 / 細胞傷害性Tfh細胞 / IgG4関連疾患 / 異所性リンパ組織 / Eomes / CD70 / 慢性炎症 / 線維化 / ミクリッツ病 / 細胞傷害性DP-Tfh細胞 / 細胞傷害性CD4T細胞 / ３次リンパ組織 / CD8 / IL-7 / Tfh細胞 / 線維性炎症 / ヒト免疫システム / Bob1 / Tfr細胞 / クラススイッチ機構 / 扁桃 / 扁桃組織 / CTL活性 / 臨床検体 / 細胞傷害活性 / 免疫関連疾患 |
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| Outline of Final Research Achievements |
This study aimed to characterize the functional features of T follicular helper cells (Tfh cells) in ectopic lymphoid tissues with chronic inflammation. The analysis of fibroinflammatory lesions of IgG4-related disease (IgG4-RD) revealed that the Tfh cell population contained double-positive Tfh cells (DP-Tfh cells), which expressed both CD4 and CD8 and presented cytotoxicity-related molecules, including Eomes, granzymes, perforin, CRTAM, and GPR56. Studies of clinical parameters and co-culture experiments using autologous T and B cells suggest that DP-Tfh cells would regulate memory B cells. Further in vitro experiments showed that normal Tfh cells could differentiate into DP-Tfh cells under the stimulation with IL-2 and IL-7, which was highly expressed in the tissue lesions of IgG4-RD. Taken together, DP-Tfh cells may play a possible role in inhibiting memory B cell function to control the antibody production program within a persistent inflammatory environment.
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| Academic Significance and Societal Importance of the Research Achievements |
Tfh細胞はリンパ濾胞胚中心の形成を調節し、抗原特異的な抗体の産生と液性免疫記憶の成立に関わるヘルパーT細胞である。臨床検体を用いた本研究から、異所性リンパ濾胞の形成を伴う３次免疫リンパ組織において細胞傷害活性を有するDP-Tfh細胞が多く検出され、B細胞による免疫記憶を調節する新たなメカニズムが示された。本研究は慢性炎症病態のさらなる理解につながり、また重症ウイルス感染症では細胞傷害性Tfh細胞が高頻度に認められるため、免疫関連疾患の病態背景のみならず、感染防御機構の研究においても意義ある成果と考えられる。
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