2003 Fiscal Year Final Research Report Summary
Analysis of the mechanism of membranous proteolysis and the immunoregulation for Sjogren's syndrome
| Project/Area Number |
12307040
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HAYASHI Yoshio The University of Tokushima, School of Dentistry, Department of Pathology, Professor, 歯学部, 教授 (00127854)
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| Project Period (FY) |
2000 – 2003
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| Keywords | Sjogren's syndrome / Apoptosis / Caspase / Autoantigen / α-fodrin / Fas Ligand / AICD / Estrogen-deficiency |
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| Research Abstract |
Primary Sjogren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/La. The purpose of this research is to elucidate the mechanisms on the development of primary Sjogren's syndrome. Although several candidate autoantigens including α-fodrin have been reported in Sjogren's syndrome, the pathogenic roles of the autoantisens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated α-fodrin proteolysis are involved in the progression of tissue destruction in Sjogren's syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death (AICD) of effector T cells may result in the development of autoimmune exocrinopathy in Sjogren's syndrome. Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens
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