2021 Fiscal Year Final Research Report
Elucidation of etiology of multiple sclerosis by gene expression control method
| Project/Area Number |
20K22905
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | 多発性硬化症 / ケモジェネティクス / ケモカイン / グレリン / アナモレリン |
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| Outline of Final Research Achievements |
Inhibitory DREADD was expressed on neurons in the thoracic spinal cord lesions of EAE mice. Neuronal silencing by inhibitory DREADD reduced CXCL10 mRNA expression in the spinal cord lesions. In in vitro migration assay, the expression of neuronal CXCL10 mRNA and migration activity of splenic CD4+ cells toward cultured embryonic cortical neurons were reduced by neuronal silencing. Intraperitoneal anamorelin, an agonist for the ghrelin receptor, administration to EAE mice mitigated their neurological severity, tended to reduce the number of lymphocytes migrated in the spinal cord lesions. Inflammatory cytokines expressed in splenic CD4+ cells from EAE mice were decreased by anamorelin treatment.
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| Free Research Field |
神経免疫
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| Academic Significance and Societal Importance of the Research Achievements |
従来、多発性硬化症において神経細胞の免疫学的作用は十分に解明されていなかった。申請者らは多発性硬化症の病態形成期において、神経細胞がCXCL10を介して、病原性CD4陽性細胞の遊走能を亢進させることを明らかにした。多発性硬化症における神経細胞の免疫細胞的作用の解明の一端となる。
グレリンの低分子アゴニストであるアナモレリンが免疫細胞に対する直接的な抗炎症作用により多発性硬化症の病態を改善させることを明らかにした。多発性硬化症における新規治療薬となる可能性がある。
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