The mechanisms for oncogenesis induced by HTLV-1-mediated modulation of cytokine signaling

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22904
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Higuchi Yusuke 熊本大学, 病院, 助教 (80882141)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: HTLV-1 / HBZ / IL-10 / STAT3

Outline of Final Research Achievements

The STAT3 D661Y mutation is frequently found in ATL cases. It was found that the STAT3 D661Y mutation binds more tightly to HBZ than wild-type STAT3. Luciferase reporter assays using SIE consensus sequence and TRE consensus sequence showed that HBZ activates not only the JAK-STAT signaling pathway but also the TGF-β signaling pathway under the coexpression of STAT3 D661Y mutant.
On the other hand, analysis of IL-10 knockout mice revealed that HBZ transgenic/IL-10 knockout mice show signs of pain and disease, such as low body weight, reduced activity, and disturbed fur, leading to early death.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

STAT3の変異はHTLV-1キャリアやATL症例に多く見られる変異の1つである。本研究ではSTAT3変異のHBZ病原性発現における意義を解析した。本研究で得られた知見は、HTLV-1病原性発現機構の解明に寄与できるものと考える。また、HBZ病原性発現にIL-10が与える影響について、生体を用いた研究を行った。これらのマウスの解析を進めることで、ATLの発症予測やATLに対する新規治療法の開発に繋がるものと考える。