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未知。尽管有人认为感染和/或组织损伤先于自身免疫的发生，但此类发生率与引发自身免疫反应之间的关系尚不清楚。在本研究中，我们发现病原体或宿主基因组释放的双链（ds）DNA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主要组织相容性复合体（MHC）和相关分子，抗原加工和呈递。这种效应是 dsDNA 特异性的，并且独立于 Toll 样受体 (TLR) 或 RIG-I，即病原体相关分子模式 (PAMP) 的已知细胞受体。我们分别表明，传统的 TLR 依赖性途径也在甲状腺中发挥作用，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配体刺激甲状腺细胞不仅激活先天免疫反应，而且导致甲状腺碘吸收和激素合成受到抑制，这与病毒感染前驱期和非感染性甲状腺功能减退症相对应。甲状腺疾病。这些证据表明，感染和/或组织损伤可以激活甲状腺的先天免疫并增强佐剂作用，从而可能引发自身免疫反应。此外，此类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）

Role of cathepsin S-dependent epithelial cell apoptosis in IFN-γ-induced alveolar remodeling and pulmonary emphysema

组织蛋白酶 S 依赖性上皮细胞凋亡在 IFN-γ 诱导的肺泡重塑和肺气肿中的作用

DOI：
10.4049/jimmunol.175.3.2026-a
发表时间：
2005-08-01
期刊：
The Journal of Immunology
影响因子：
0
作者：
A. Flavell;J. Schmidt;J. A. Elias;Desanctis;S. Underwood;M. Graupe;Richard;Chapman;R. Homer;D. Aldous;George;W. Liu;C. Lee;Lesley A. Rabach;A. Harold;T. Zheng;M. Kang;K. Crothers;Zhou Zhu
通讯作者：
Zhou Zhu

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

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Rocchi R
通讯作者：
Rocchi R

High expression levels of Mycobacterium leprae pseudogenes are altered upon infection.

麻风分枝杆菌假基因的高表达水平在感染后发生改变。

DOI：
发表时间：
2006
期刊：
影响因子：
2.1
作者：
Suzuki K; Nakata N; Pham DB; Ishii N; Makino M.
通讯作者：
Makino M.

Toll-like receptor adaptor molecules enhance DNA-raised adaptive immune responses against influenza and tumors through activation of innate immunity.

Toll 样受体接头分子通过激活先天免疫增强 DNA 引发的针对流感和肿瘤的适应性免疫反应。

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
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.
通讯作者：
Sasaki S.

Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa.

多价 DNA 疫苗可保护小鼠免受铜绿假单胞菌引起的肺部感染。