2020 Fiscal Year Final Research Report
Molecular mechanisms of neuropsychiatric lupus pathogenesis and development of novel therapies
| Project/Area Number |
19K17900
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | 全身性エリテマトーデス / 精神神経ループス / ミクログリア / 活性化 |
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| Outline of Final Research Achievements |
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that causes multi-organ dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30-40% of lupus patients and is one of the most severe organ lesions of SLE, sometimes resulting in chronic complications. Recent papers have shown that microglia, tissue-resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. We examined the microglial activation in MRL/lpr, lupus-prone mice, and the effect of stimulation with cytokines for microglia using RNA sequencing.
Microglia from MRL/lpr were activated than those from control mice. The results of RNA-Seq had revealed that several new therapeutic target in NPSLE. Intracerebroventricular administration of an inhibitor of gene X ameliorated the disease activity of NPSLE.
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| Free Research Field |
自己免疫性疾患
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| Academic Significance and Societal Importance of the Research Achievements |
NPSLEはSLE患者の20-40％に認められ、意識障害やてんかんなどを呈する。一部の患者では高次機能障害などが残存したり、またうつ病症状などから自殺に至る場合もあり、SLEのアンメットニーズの一つとなっている。またNPSLEの後遺症により内服薬のコンプライアンスが悪くなることも知られており、NPSLEはSLEの予後規定因子のひとつと考えられている。しかしその詳細は不明であり、エビデンスのある治療戦略も立てられていないのが現状である。本研究はNPSLEの新たな病態を明らかにし、新規治療薬への開発とつながる可能性がある。
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