Molecular mechanism and regulation in Sjogren's syndrome

干燥综合征的分子机制及调控

• 批准号: 21591260
• 负责人: SUMIDA Takayuki
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591260/
• 关键词: 膠原病学; シェーグレン症候群; T細胞; 自己抗体; T細胞エピトープ; アナログペプチド; M3R; 自己免疫性唾液腺炎; 抗原特異的制御; IFN-γ; IL-17; ムスカリン作働性アセチルコリン受容体(M3R); 抗M3R抗体; M3Rペプチド; M3R誘導唾液腺炎モデルマウス; 抗原特異的治療

Sjogren's syndrome (SS) is one of autoimmune diseases. The purpose of this study is to clarify the molecular mechanism in the pathogenesis of SS and establish the new therapeutic strategy against target molecule. In this research, we focused on Muscarinic acetylcholine receptor 3 (M3R), because this receptor is a functional molecule to produce saliva from salivary glands. Our results are followings. 1) There were anti-M3R autoantibodies and M3R reactive T cells in about 50% of patients with SS. 2) The B cell epitopes were on N region, the first, the second, and the third extra-cellular domains of M3R molecules. 3) Antibodies against the second extracellular domain of M3R were the pathogenic autoantibody to suppress the saliva production. 4) We established M3R immunized sialadenitis (MIS) mouse model using M3RKO mouse and Rag-1KO mouse. 5) IFN-γand/or IL-17 producing M3R reactive T cells were necessary to generate MIS. 6) The dominant T cell epitope of M3R was the first extracellular domain to induce MIS. Now we are selecting APL of T cell epitope and near future try to control MIS and SS via antigen-specific therapeutic strategy.

干燥综合征（SS）是自身免疫性疾病之一，本研究的目的是阐明SS发病的分子机制并建立针对靶分子的新治疗策略。本研究重点关注毒蕈碱乙酰胆碱受体3（M3R）。 ），因为该受体是唾液腺产生唾液的功能分子，我们的结果如下：1）体内存在抗M3R自身抗体和M3R反应性T细胞。约50%的SS患者。 2) B细胞表位位于M3R分子的第一、第二和第三胞外结构域上。 3) 针对M3R第二胞外结构域的抗体是致病性自身抗体。 4）我们使用M3RKO小鼠和Rag-1KO小鼠建立了M3R免疫唾液腺炎（MIS）小鼠模型。5）IFN-γ和/或。产生 M3R 反应性 T 细胞是产生 MIS 所必需的。 6) M3R 的主要 T 细胞表位是诱导 MIS 的第一个细胞外结构域。现在我们正在选择 T 细胞表位的 APL，并在不久的将来尝试控制 MIS 和 SS。通过抗原特异性治疗策略。

项目成果

Six-transmembrane epithelial antigen of prostate4 (STEAP4) is a tumor necrosis factor alpha-induced protein that regulates IL-6, IL-8, and cell proliferation in synovium from patients with rheumatoid arthritis

前列腺六跨膜上皮抗原 4 (STEAP4) 是一种肿瘤坏死因子 α 诱导蛋白，可调节类风湿性关节炎患者滑膜中的 IL-6、IL-8 和细胞增殖

• 发表时间: 2012
• 作者: Tanaka; Y.; Matsumoto; I.; Iwanami; K.; Inoue; A.; Umeda; N.; Sugihara; M.; Hayashi; T.; Ito; S.; Sumida; T.
• 通讯作者: T.

Efficacy of mizoribine pulse therapy inrheumatoid arthritis patients with reducedor insufficient response to infliximab

米佐立宾冲击治疗对英夫利昔单抗反应减弱或不足的类风湿性关节炎患者的疗效

• 发表时间: 2009
• 作者: Horikoshi; M.; Ito; S.; Ishikawa; M.; Umeda; N.; Kondo; Y.; Tsuboi; H.; Hayashi; T.; Goto; D.; Matsumoto; I.;Sumida; T
• 通讯作者: T

A case ofatypical Cogan's syndrome with arortitis

伴有主动脉炎的非典型Cogan综合征1例

• 发表时间: 2009
• 作者: Kondo; Y.; Ito; S.; Oi; Y.; Satou; H.; Tsuboi; H.; Sugihara; M.; Hayashi; T.; Goto; D.; Matsumoto; I.;Sumida; T
• 通讯作者: T

Inhibition of transforming growth factor‐β signalling attenuates interleukin (IL)‐18 plus IL‐2‐induced interstitial lung disease in mice

抑制转化生长因子αβ信号可减轻白细胞介素 (IL)α18 加 ILα2 诱导的小鼠间质性肺疾病

• DOI: 10.1111/j.1365-2249.2010.04094.x
• 发表时间: 2010-06-01
• 期刊: Clinical & Experimental Immunology
• 影响因子: 4.6
• 作者: S. Segawa;D. Goto;Y. Yoshiga;Makoto Sugihara;Taichi Hayashi;Y. Chino;Isao Matsumoto;Satoshi Ito;Takayuki Sumida
• 通讯作者: Takayuki Sumida

Analysis of Gender Differences in Genetic Risk: Association of TNFAIP3 Polymorphism with Male Childhood-Onset Systemic Lupus Erythematosus in the Japanese Population

遗传风险的性别差异分析：TNFAIP3 多态性与日本人群中男性儿童期发病的系统性红斑狼疮的关联

• DOI: 10.1371/journal.pone.0072551
• 发表时间: 2013-08-30
• 期刊: PLoS ONE
• 影响因子: 3.7
• 作者: Keisuke Kadota;M. Mori;M. Yanagimachi;T. Miyamae;Takuma Hara;T. Kanetaka;T. Nozawa;M. Kikuchi;Ryoki Hara;T. Imagawa;T. Kaneko;S. Yokota
• 通讯作者: S. Yokota