| Project/Area Number |
19K08843
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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 54010:Hematology and medical oncology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
Mizuguchi Mariko 琉球大学, 医学(系)研究科(研究院), 助教 (40581541)
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| Co-Investigator(Kenkyū-buntansha) |
田中 勇悦 琉球大学, 医学部, 産学官連携研究員 (30163588)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | HTLV-1 / ATL / OX40 / OX40L / FOXP3 / Foxp3 |
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| Outline of Research at the Start |
成人T細胞白血病 (ATL)は、ヒトT細胞白血病ウイルス1型 (HTLV-1)がCD4陽性T細胞に感染し、長期の潜伏期を経て発症する。ATL患者では、免疫抑制能を有するFoxp3陽性の制御性T細胞 (Treg)の異常増殖が見られ、それがATL発病に深く関与することが示唆されている。本研究では、患者ATL細胞において、HTLV-1感染に起因するOX40L/OX40系の活性化が選択的なFoxp3陽性Treg細胞の異常増殖および生存に寄与するかを明らかにする。
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| Outline of Final Research Achievements |
Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignant disease of mature T-cells caused by human T-cell leukemia virus type-1 (HTLV-1) infection. ATL cells express the transcription factor FOXP3, which is primarily expressed in regulatory T-cells (Tregs). Normal Treg cells differentiate and expand through the activation of OX40 signaling. To elucidate the mechanisms underlying the expansion of FOXP3+ HTLV-1-infected cells, the expression of OX40 and its ligand OX40L on ATL cells were examined. Flow cytometric analysis showed that FOXP3+ cells expressed OX40, while FOXP3- cells expressed OX40L. OX40 signaling was found to be involved in the expression of genes related to anti-apoptosis and cell growth. Furthermore, the deprivation of OX40 and OX40L resulted in inhibited cell growth in HTLV-1-infected cells. These findings suggest that the interaction between FOXP3- OX40L+ cells and FOXP3+ OX40+ ATL cells stimulates the proliferation of FOXP3+ ATL cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果より、HTLV-1感染者体内に存在するFOXP3- OX40L+ 細胞とFOXP3+ OX40+ ATL細胞がお互いに接触反応することにより、FOXP3+ ATL細胞の増殖が促進される可能性が示唆された。
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