2006 Fiscal Year Final Research Report Summary
Changes in gene expression profile and development of autoimmunity in the thyroid following infection.
| Project/Area Number |
15390296
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | National Institute of Infectious Diseases |
|---|
Principal Investigator |
SUZUKI Koichi National Institute of Infectious Diseases, Department of Bioregulation, Chief, 生体防御部, 室長 (20206478)
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2003 – 2006
|
| Keywords | Thyroid / Infection / Autoimmunity / dsDNA / TLR / Innate immunity |
|---|
| 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.
|
Research Products
(46 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] A TLR-independent antiviral response induced by double-stranded B-DNA.2006
Author(s)
Ishii KJ, Coban C, Kato K, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sto S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S.
-
Journal Title
Nat Immunol 7(1)
Pages: 40-48
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity.2006
Author(s)
Takeshita F, Tanaka T, Matsuda T, Tozuka M, Takase K, Saha S, Matsui K, Ishii KJ, Coban C, Akira S, Ishii N, Suzuki K, Klinman DM, Okuda K, Sasaki S.
-
Journal Title
J Virol. 80
Pages: 6218-6224
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF.2005
Author(s)
Takeshita F, Ishii KJ, Kobiyama K, Kojima Y, Coban C, Sasaki S, Ishii N, Klinman DM, Okuda K, Akira S, Suzuki K.
-
Journal Title
Eur J Immunol 35(8)
Pages: 2477-2485
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
[Journal Article] Mechanism of iodide/chloride exchange by Pendrin.2004
Author(s)
Yoshida A, Hisatome I, Taniguchi S, Sasaki N, Yamamoto Y, Miake J, Fukui H, Shimizu H, Okamura T, Okuda T, Igawa O, Green ED, Kohn LD, Suzuki K.
-
Journal Title
Endocrinology 145
Pages: 4301-4308
Description
「研究成果報告書概要(欧文)」より
-
-
[Journal Article] The 90k protein increases MHC class I expression and is regulated by hormones, y-interferon and double strand polynucleotides.2004
Author(s)
Grassadonia A, Tinari N, Fiorentino B, Suzuki K, Nakazato M, De Tursi M, Giuliani C, Napolitano G, Singer DS, Iacobelli S, Kohn LD.
-
Journal Title
Endocrinology 145
Pages: 4727-4736
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
