Roles of OX40/OX40L in ATL
| 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
|
| Project Status |
Completed (Fiscal Year 2022)
|
| 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)
|
|---|
| Keywords | HTLV-1 / ATL / OX40 / OX40L / FOXP3 / Foxp3 |
|---|
| 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。
|
| 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.
|
| 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。
|
Report
(5 results)
Research Products
(18 results)
-
-
[Journal Article] Elevation of the Plasma Levels of TNF Receptor 2 in Association with Those of CD25, OX40, and IL-10 and HTLV-1 Proviral Load in Acute Adult T-Cell Leukemia2022
Author(s)
Megumi Kato, Naoki Imaizumi, Reiko Tanaka, Mariko Mizuguchi, Masaki Hayashi, Takashi Miyagi, Junnosuke Uchihara, Kazuiku Ohshiro, Junpei Todoroki, Kennosuke Karube, Hiroaki Masuzaki, Yuetsu Tanaka, Takuya Fukushima
-
Journal Title
Viruses
Volume: 14
Issue: 4
Pages: 751-751
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Acute type adult T-cell leukemia cells proliferate in the lymph nodes rather than in peripheral blood2022
Author(s)
Mariko Mizuguchi, Mitsuyoshi Takatori, Shugo Sakihama, Manami Yoshita-Takahashi, Naoki Imaizumi, Yoshiaki Takahashi, Hiroo Hasegawa, Kennosuke Karube, Takuya Fukushima, Masataka Nakamura, Yuetsu Tanaka
-
Journal Title
Cancer Gene Therapy
Volume: -
Issue: 11
Pages: 1570-1577
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue.2020
Author(s)
Kato H, Okabe K, Miyake M, Hattori K, Fukaya T, Tanimoto K, Beini S, Mizuguchi M, Torii S, Arakawa S, Ono M, Saito Y, Sugiyama T, Funatsu T, Sato K, Shimizu S, Oyadomari S, Ichijo H, Kadowaki H, Nishitoh H.
-
Journal Title
Life science alliance
Volume: 3
Issue: 3
Pages: 201900576-201900576
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
-
[Presentation] 急性型ATL患者の末梢ATL細胞は増殖しない.2021
Author(s)
水口真理子, 高鳥光徳, 崎浜秀悟, 髙橋真奈美, 今泉直樹, 高橋良明, 長谷川寛雄, 加留部謙之輔, 福島卓也, 中村正孝, 田中勇悦
Organizer
第7回日本HTLV-1学術集会
Related Report
-
-
-
-
-
-
-
-
-
