Evaluation of immune suppressive therapy using autoimmune model mouse

使用自身免疫模型小鼠评价免疫抑制治疗

• 批准号: 12557072
• 负责人: NISHIKAWA Takeji
• 金额: $ 8.45万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557072/
• 关键词: Autoimmune; Autoantibody; Model mouse; Pemphigus; desmoglein; Immune suppression; Therapy; cadherin; 天庖瘡

Treatment regime for rare diseases, such as autoimmune diseases, are mostly based on personal experiences and each treatment lacks objective evaluation. This is largely due to the lack of animal models which well mimic the corresponding human diseases. We have recently developed a novel active disease mouse model using autoantigen knockout mouse, which does not require immune tolerance against the defective autoantigen. The purpose of this study is to develop an evaluation system of various immune suppressive therapeutic strategies using the autoimmune disease mouse model. Dsg3 -/- mice, which originally had a mixed genetic background of 129 and C57BL/6 mouse, were backcrossed to C57BL/6 and Balb/C mouse by 10 generation to reduce the difference of immune response of each individual mouse. A large mouse colony was established to supply a sufficient number of model mice for this assay. An objective score to evaluate the disease activity of the model mouse considering number of skin lesions, weight loss and patchy hair loss. The usefulness of our system was confirmed by evaluating a novel therapeutic strategy using anti-CD40L monoclonal antibody. In the future various therapeutic strategies will be evaluated with our system using the model mouse

罕见病（如自身免疫性疾病）的治疗方案大多基于个人经验，每种治疗缺乏客观评估。这在很大程度上是由于缺乏很好地模拟相应人类疾病的动物模型。我们最近开发了一种新的活动性疾病的小鼠模型，使用自身抗原敲除小鼠，它不需要对缺陷的自身抗原的免疫耐受。本研究的目的是利用自身免疫性疾病小鼠模型建立一个评价各种免疫抑制治疗策略的系统。Dsg 3-/-小鼠最初具有129和C57 BL/6小鼠的混合遗传背景，与C57 BL/6和Balb/C小鼠回交10代，以减少每个个体小鼠的免疫应答差异。建立了一个大的小鼠群体，以提供足够数量的模型小鼠用于本试验。考虑皮肤病变数量、体重减轻和斑片状脱毛，评价模型小鼠疾病活动的客观评分。我们的系统的有用性得到证实，通过评估一种新的治疗策略，使用抗CD 40 L单克隆抗体。在未来的各种治疗策略将评估与我们的系统使用的模型小鼠

项目成果

Cheng SW, Kobayashi M, Tanikawa A, Kinoshita-Kuroda K, Amagai M: "Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3"Br J Dermatol. (in press). (2002)

Cheng SW、Kobayashi M、Tanikawa A、Kinoshita-Kuroda K、Amagai M：“使用重组桥粒芯糖蛋白 1 和 3 通过酶联免疫吸附测定监测天疱疮的疾病活动”Br J Dermatol。

Sekiguchi M, Futei Y, Fujii Y, Iwasaki T, Nishikawa T, Amagai M: "Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins"J Immunol. 167. 5439-5448 (2001)

Sekiguchi M、Futei Y、Fujii Y、Iwasaki T、Nishikawa T、Amagai M：“天疱疮抗体识别的显性自身免疫表位映射到桥粒芯糖蛋白的 N 末端粘合区域”J 免疫学杂志。

Futei Y., Amagai M., Ishii K., Kuroda-Kinoshita K., Ohya K., Nishikawa T.: "Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus"J Dermatol Sci. 26. 55-61 (2001)

Futei Y.、Amagai M.、Ishii K.、Kuroda-Kinoshita K.、Ohya K.、Nishikawa T.：“寻常型天疱疮和落叶型自身抗体中的主要 IgG4 亚类”J Dermatol Sci。

sekiguchi M, Futei Y, Fujil Y, Iwasaki T, Nishikawa T, Amagai M: "Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins"J Immunol. 167. 5439-5448 (2001)

sekiguchi M、Futei Y、Fujil Y、Iwasaki T、Nishikawa T、Amagai M：“天疱疮抗体识别的显性自身免疫表位映射到桥粒芯糖蛋白的 N 末端粘合区域”J 免疫学杂志。

Ohyama M, Amagai M, Tsunoda K, Ota T, Koyasu S, Umezawa A, Hata J: "Immunologic and histopathologic characterization of active disease mouse model for pemphigus vulgaris"J Invest Dermatol. 118. 199-204 (2002)

Ohyama M、Amagai M、Tsunoda K、Ota T、Koyasu S、Umezawa A、Hata J：“寻常型天疱疮活动性疾病小鼠模型的免疫学和组织病理学特征”J Invest Dermatol。