Immunotherapeutic analysis using newly established murine models for Sjogren' s syndrome

使用新建立的干燥综合征小鼠模型进行免疫治疗分析

• 批准号: 21249090
• 负责人: HAYASHI Yoshio
• 金额: $ 29.54万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 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/en/grant/KAKENHI-PROJECT-21249090/
• 关键词: シェーグレン症候群; 自己免疫疾患; 治療法開発; RbAp48; CCR7; エストロゲン; アロマターゼ; RNA干渉; カテプシンL

We reported that transgenic(TG) expression of RbAp48, and CCR7 knockout(KO) mice resulted in the development of autoimmune exocrinopathy resembling Sjogren' s syndrome. CD4^+ T cell-mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γand interleukin-18, which activates interferon regulatory factor-1(IRF-1), and class II transactivator(CIITA). Regulatory T(Treg) cells were significantly retained in the lymph nodes of CCR7KO mice, and failed to patrol within the exocrine organs to protect autoimmunity. The gene targeting for RbAp48 with application of in vivo siRNA administration prevented autoimmune lesions. These results indicate a novel immunocompetent role of epithelial cells, resulting in loss of local tolerance prior to developing gender-based autoimmunity.

我们报道了RBAP48和CCR7敲除（KO）小鼠的转基因（TG）表达导致自身免疫性外分泌性疾病类似于Sjogren综合征。 CD4^+ T细胞介导的自身免疫性病变与自身抗体生产有关。我们获得了唾液上皮细胞可以产生干扰素-γ和白细胞介素-18的证据，该细胞激活了干扰素调节因子1（IRF-1）和II类反式激活剂（CIITA）。调节性T（Treg）细胞在CCR7KO小鼠的淋巴结中显着保留，并且未能在外分泌器官中巡逻以保护自身免疫性。使用体内siRNA给药的RBAP48的基因靶向可阻止自身免疫性病变。这些结果表明上皮细胞的新型免疫能力作用，导致在发展基于性别的自身免疫性之前失去局部耐受性。

项目成果

YKL-40 secreted from adipose tissue inhibits degradation of type I collagen

• DOI: 10.1016/j.bbrc.2009.08.024
• 发表时间: 2009-10-23
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Iwata, Takeo;Kuwajima, Masamichi;Yoshimoto, Katsuhiko
• 通讯作者: Yoshimoto, Katsuhiko

Real-time in vivo imaging of p16Ink4a reveals cross talk with p53.

• DOI: 10.1083/jcb.200904105
• 发表时间: 2009-08-10
• 期刊: The Journal of cell biology
• 作者: Yamakoshi K;Takahashi A;Hirota F;Nakayama R;Ishimaru N;Kubo Y;Mann DJ;Ohmura M;Hirao A;Saya H;Arase S;Hayashi Y;Nakao K;Matsumoto M;Ohtani N;Hara E
• 通讯作者: Hara E

シェーグレン症候群における調節性T細胞の役割

调节性 T 细胞在干燥综合征中的作用

• 发表时间: 2010
• 作者: Yamada;E.;Inoue;C.;Oda;K.;Kobayashi;T.;Hayashi;Y.,Onbe;H.;Yokoyama;E.;Shimomura;Y.;Kawaguchi;T.;石丸直澄
• 通讯作者: 石丸直澄

Critical Signaling Pathway via CCR7 of Foxp3+CD25+CD4+ Regulatory T Cells for the Egress from Lymph Nodes

Foxp3 CD25 CD4 调节性 T 细胞通过 CCR7 进行淋巴结出口的关键信号通路

• 发表时间: 2010
• 作者: 大西和子;辻川真弓;吉田和江;後藤姉奈;町本美保;大石ふみ子;山田章子;石丸直澄
• 通讯作者: 石丸直澄

A novel role of NFkB relB in bone remodeling

NFkB relB 在骨重塑中的新作用

• 发表时间: 2011
• 作者: Gao;J.;Takeuchi;H.;Zhao;Z.;Fujii;M.;Kanematsu;T. and Hirata;M.;Masahiro Hiasa
• 通讯作者: Masahiro Hiasa