2006 Fiscal Year Final Research Report Summary
Functional analysis ofAIRE, a gene responsible for the hereditary type of autoimmune disease
| Project/Area Number |
17390291
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MATSUMOTO Mitsuru The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (60221595)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Noriyuki The University of Tokushima, Institute for Enzyme Research, Assistant Professor, 分子酵素学研究センター, 助手 (50359915)
OSHIKAWA Kiyotaka The University of Tokushima, Institute for Enzyme Research, COE Investigator, 分子酵素学研究センター, COE研究員 (50380051)
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| Project Period (FY) |
2005 – 2006
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| Keywords | AIRE / autoimmune disease / self-tolerance / thymus / NOD mic |
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| Research Abstract |
Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type I diabetes caused by autoimmune attack against b-cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than β-cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of auto-Ab against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathologic change, the animals were resistant to the development of diabetes. The results suggest that Aire is not only critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T-cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.
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Research Products
(11 results)
