Roles of OX40/OX40L in ATL

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: Mizuguchi Mariko 琉球大学, 医学(系)研究科(研究院), 助教 (40581541)
• Co-Investigator(Kenkyū-buntansha): 田中 勇悦 琉球大学, 医学部, 産学官連携研究員 (30163588)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: HTLV-1 / ATL / OX40 / OX40L / FOXP3

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.

Free Research Field

分子生物学

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。