| Project/Area Number |
15390296
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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 |
Endocrinology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
SUZUKI Koichi National Institute of Infectious Diseases, Department of Bioregulation, Chief, 生体防御部, 室長 (20206478)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Fumihiko Yokohama City University, Department of Molecular Biodefense Research, Associate professor, 分子生体防御学, 准教授 (60333572)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Thyroid / Infection / Autoimmunity / dsDNA / TLR / Innate immunity / B-DNA / Toll様受容体 / dsRNA / ヨード / ホルモン合成 / ルシフェラーゼ / MHC / サイログロブリン / インターフェロン / バセドウ病 |
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| Research Abstract |
Pathological basis of autoimmune thyroid diseases are still largely unknown. Although it has been suggested that infection and/or tissue damage precede the onset of autoimmunity, the relationship between such incidences and the triggering of autoimmune reactions was not clear. In the present study, we have shown that double-stranded (ds) DNA released from pathogen or host genome acts on thyroid cells to produce type I interferons, proinflammatory cytokines and chemokines as well as major histocompatibility complex (MHC) and related molecules necessary for antigen processing and presentation. This effect was dsDNA-specific and independent of toll-like receptors (TLRs) or RIG-I, known cellular receptors for pathogen-associated molecular patterns (PAMPs). We separately showed that conventional TLR-dependent pathways are also operating in the thyroid and involved in the initiation of innate immune reaction. TLRs are indeed expressed in the thyroid follicular epithelium and in mast cells in the gland. Interestingly, stimulation of thyroid cells by dsDNA or TLR ligands not only activated innate immune reactions, but resulted in suppression of iodide uptake and hormone synthesis of the thyroid, which is corresponding to the thyroid dysfunction seen in the prodromal period of viral infection and non-thyroid illness. These evidence suggest that infection and/or tissue damage can activate innate immunity in the thyroid and enhance the adjuvant effect, which may trigger autoimmune reactions. Additionally, such events may be a direct cause of thyroid dysfunction.
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