A study on immunological abnormality in the lysosomal storage disease
| Project/Area Number |
17590355
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Yokohama City University |
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Principal Investigator |
YAMANAKA Shoji Yokohama City Univeristy Hospital, Associate Professor, 附属病院, 準教授 (80264604)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Akira Yokohama City University, School of Medicine, Research Fellow, 医学部, 研究員 (20381585)
AOKI Ichiro Yokohama City University, School of Medicine, Professor, 医学研究科, 教授 (00184028)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Sandhoff disease / lysosomal storage disease / autoimmune disease / hexosaminidase / 免疫異常 / 胸腺 / リンパ球 / マクロファージ |
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| Research Abstract |
Sandhoff disease (SD), a prototype of lysosomal storage diseases, is a severe neurodegenerative disorder caused by mutations in the HEXB gene coding for the β subunit of the lysosomal hexosaminidases A and B. HEXB mutations result in the accumulation of undegraded substrates such as GM2 and GA2 in lysosomes.
Neurological abnormalities have been ascribed in part to neuronal cell death caused by the accumulation of both undigested GM2 gangliosides and related lipids in neuronal lysosomes. However, several recent investigations have suggested that ganglioside accumulation in neurons alone cannot completely explain the nerve cell damage and the short life span. Recently we and others have reported several immunological abnormalities in the CNS which would lead to neuronal cell death. In this study we focused on thymic event from the point of morphology, flow cytometry, and microarray analysis to see the autoimmune mechanisms happening in SD mice.
In the terminal stage of SD mice, marked thymic involution was noted both macroscopically and microscopically. The number of T lymphocyte in the cortex was decresed and macophage was markedly increased. T lymphocytes contained IgG on their cell surface. Macophages were swollen with nuclear fragments and undegraded GM2 and GA2 in the cytoplasm.
The microarray data showed upregulation of B cell-related genes, macrohage-related genes, chemokines and TH2-related genes.
From these results, macrophages englobe IgG-bearing T lymphocytes via autoimmune mechanisms and lead to GM2 and GA2 accumulation. As a results, macrophages are activated to facilitate autoimmune mechanisms.
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Report
(3 results)
Research Products
(8 results)
