Molecurar immunological study of VKH disease

VKH病的分子免疫学研究

• 批准号: 11671722
• 负责人: YAMAKI Kunihiko
• 金额: $ 2.24万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671722/
• 关键词: Tyrosinase; Transgenic rats; MHC; Expression

We have reported that tyrosinase family protein can induce autoimmune disease similar to Vogt-Koyanagi Harada disease (VKH). The lymphocytes from PBMC with VKH disease patients proliferate against tyrosinase family proteins. These results suggest that tyrosinase family proteins are antigens specific to VKH.In this project, we further confirmed these results and studied the immune reactions involved in VKH.To clarify the development and differentiation of autoreactive T cells in VKH, we are now making the transgenic Lewis rats expressing tyrosinase. Lewis rats lacks the tyrosinase, but are sensitive to the various kind of autoimmune disease. The Lewis rats that express tyrosinase in different organs and periods will be effective to study the central and peripheral tolerance against autoantigens.We are planing to make the transgenic rats that will express tyrosinase under the promoter of arrestin for retina specific expression, β-actin for ubiquitous expression and tyrosinase for melanocyte. We are now making the siblings of the rats bearing the transgene.

我们已经报道酪氨酸酶家族蛋白可以诱导类似于Vogt-Koyanagi Harada病（VKH）的自身免疫性疾病。VKH病患者PBMC中的淋巴细胞对酪氨酸酶家族蛋白具有增殖作用。本研究进一步证实了酪氨酸酶家族蛋白是VKH的特异性抗原，并对VKH参与的免疫反应进行了研究，为了阐明VKH中自身反应性T细胞的发育和分化，我们正在制备表达酪氨酸酶的转基因刘易斯大鼠。刘易斯大鼠缺乏酪氨酸酶，但对各种自身免疫性疾病敏感。在不同器官和时期表达酪氨酸酶的刘易斯大鼠将有效地研究中枢和外周对自身抗原的耐受性。我们计划在视网膜特异性表达的抑制蛋白、普遍表达的β-肌动蛋白和黑素细胞酪氨酸酶的启动子下制备表达酪氨酸酶的转基因大鼠。我们现在正在制造携带转基因的老鼠的兄弟姐妹。

项目成果

Kunihiko Yamaki, Kiyoko Gocho, KOichi Hayakawa, Isao Kondo, and Shozo Sakuragi.: "Tyrosinase Family Proteins Are Antigens Specific to Vogt-Koyanagi-Harada Disease."The Journal of Immunology. 165. 7323-7329 (2000)

Kunihiko Yamaki、Kiyoko Gocho、KOichi Hayakawa、Isao Kondo 和 Shozo Sakuragi。：“酪氨酸酶家族蛋白是 Vogt-小柳-原田病的特异性抗原。”免疫学杂志。

KUNIHIKO YAMAKI: "Ocular and Extraocular Inflammation Induced by Immunization of Tyrosinase Related Protein land 2 Lewis Rats"EXPERIMENTAL EYE RESEARCH. 71. 361-369 (2000)

KUNIHIKO YAMAKI：“酪氨酸酶相关蛋白和 2 只路易斯大鼠免疫诱导的眼部和眼外炎症”实验眼科研究。

KUNIHIKO YAMAKI: "Tyrosinase Family Proteins Are Antigens Specific to Vogt-Koyanagi-Harada Disease"The Journal of Immunology. 165. 7323-7329 (2000)

KUNIHIKO YAMAKI：“酪氨酸酶家族蛋白是 Vogt-小柳-原田病的特异性抗原”免疫学杂志。

Kunihiko Yamaki, Isao Kondo, Hideo Nakamura, Mika Miyano, Seiki Konnno, and Synozo Sakuragi.: "Ocular and Extraocular Inflammation Induced by Immunization of Tyrosinase Related Protein 1 and 2 in Lewis Rats."Experimental Eye Reseach. 71. 361-369 (2000)

Kunihiko Yamaki、Isao Kondo、Hideo Nakamura、Mika Miyano、Seiki Konnno 和 Synozo Sakuragi。：“路易斯大鼠中酪氨酸酶相关蛋白 1 和 2 免疫诱导的眼部和眼外炎症。”实验眼科研究。

KUNIHIKO YAMAKI: "Ocular and Extraocular Inflammation Induced by Immunization of Tyrosinase Related Protein 1 and 2 in Lewis Rats"EXPERIMENTAL EYE RESEARCH. 71. 361-369 (2000)

KUNIHIKO YAMAKI：“路易斯大鼠中酪氨酸酶相关蛋白 1 和 2 免疫诱导的眼部和眼外炎症”实验眼科研究。