Study of inflammatory loop mechanism caused by virus-infected cells in HAM pathogenesis.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09701
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Araya Natsumi 聖マリアンナ医科大学, 医学研究科, 助教 (80440353)
• Research Collaborator: Takahashi Katsunori
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: HTLV-1 / HAM / CXCL10 / CXCR3 / 炎症

Outline of Final Research Achievements

From recent our studies, we suggested that the cross-talk between HTLV-1-infected cells and CXCL10 produced from astrocytes in the spinal cord is important for the formation and maintenance of HTLV-1-related myelopathy (HAM). In this study, to test this hypothesis, I analyzed the HAM model mice which were created by implanting HAM-PBMC into the most highly immunodeficient mice that express CXCL10 specifically in the central nervous system (HAM-PBMC-NSG/GFAP-CXCL10 mice). As results, I proved the infiltration of lymphocytes and infected cells into the central nervous system in HAM-PBMC-NSG/GFAP-CXCL10 mice.
In the future, we intend to prove the usefulness as a HAM disease state analysis model by establishing the similarities between the mouse and the HAM disease state by detailed analysis.

Free Research Field

分子細胞免疫学

Academic Significance and Societal Importance of the Research Achievements

HAMは先進国の中でその患者が多いのは日本のみであるため、HAMの病態や発症予防法・治療法に関する我が国での研究成果は世界中から期待されておりその責任は重い。未だHAMには有効な治療法が無く、新規治療薬開発が強く要望されている。HAM 治療法の開発には、ヒトのHAM病態を忠実に再現した動物モデルの必要性が高い。これまでに感染T細胞の細胞浸潤に起因する脊髄障害をきたすHAM病態を再現した動物は得られていない。本研究では、世界初のヒト免疫系を再現したHAMモデルマウスの作製を目指し、HAM病態機序の解明、疾患の診断、予防、治療法の発展に寄与したいと考える。