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Changes in gene expression profile and development of autoimmunity in the thyroid following infection.

感染后甲状腺基因表达谱的变化和自身免疫的发展。

基本信息

批准号：
15390296
负责人：
SUZUKI Koichi
金额：
$ 8万
依托单位：
National Institute of Infectious Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

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.

自身免疫性甲状腺疾病的病理基础仍然很大程度上是未知的。虽然有研究表明感染和/或组织损伤先于自身免疫的发生，但这种情况与自身免疫反应的触发之间的关系尚不清楚。在本研究中，我们发现从病原体或宿主基因组释放的双链DNA （ds）作用于甲状腺细胞，产生I型干扰素、促炎细胞因子和趋化因子，以及抗原加工和递呈所必需的主要组织相容性复合体（MHC）和相关分子。这种效应是dsdna特异性的，独立于toll样受体（TLRs）或rig - 1，已知的病原体相关分子模式（PAMPs）的细胞受体。我们分别表明，传统的tlr依赖途径也在甲状腺中起作用，并参与先天免疫反应的启动。tlr确实在甲状腺滤泡上皮和腺体肥大细胞中表达。有趣的是，dsDNA或TLR配体对甲状腺细胞的刺激不仅激活了先天免疫反应，而且抑制了甲状腺的碘吸收和激素合成，这与病毒感染和非甲状腺疾病前驱期的甲状腺功能障碍相对应。这些证据表明，感染和/或组织损伤可激活甲状腺的先天免疫，增强辅助作用，从而可能引发自身免疫反应。此外，这些事件可能是甲状腺功能障碍的直接原因。

项目成果

期刊论文数量（69）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A fused gene of nucleoprotein(NP) and herpes simplex virus genes(VP22) induces highly protective immunity against different subtypes of influenza virus

核蛋白（NP）和单纯疱疹病毒基因（VP22）的融合基因可诱导针对不同亚型流感病毒的高度保护性免疫

DOI：
发表时间：
2006
期刊：
Virology 35
影响因子：
0
作者：
Saha S;Yoshida S;Ohba K;Matsui K;Matsuda T;Takeshita F;Umeda K;Tamura Y;Okuda K;Klinman D;Xin KQ;and Okuda K
通讯作者：
and Okuda K

Toll-like receptor-MyD88 and Fe receptor pathways of mast cells mediate the thyroid dysfunctions observed during nonthyroidal illness

肥大细胞的 Toll 样受体 MyD88 和 Fe 受体途径介导非甲状腺疾病期间观察到的甲状腺功能障碍