Establishment of murine model of eosinophil-infiltrating drug photoallergy and elucidation of its immunological mechanism

嗜酸性粒细胞浸润药物光过敏小鼠模型的建立及其免疫机制的阐明

• 批准号: 18591267
• 负责人: TOKURA Yoshiki
• 金额: $ 2.4万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591267/
• 关键词: drug; photosensitivity; ultraviolet light; eosinophil; lymphocyte

We established a murine model of the eosinophil-infiltrating type of drug photoallergy by using afloqualone (AQ), a representative photosensitive drug. AKR/J mice were sensitized by an i.p. injection of afloqualone solution and irradiation of shaved abdomen with UVA. This sensitization procedure was repeated 2-12 times (twice a week), and 3 days after the last immunization, mice were challenged by an s.c. injection of AQ solution and irradiation of the same site with UVA. Mice receiving more than 10 times of sensitization exhibited a massive infiltrate of eosinophils and lymphocytes at the challenged site. This reaction was AQ photoantigen-specific, and AKR/J mice were a high responder strain of this sensitivity. The sensitivity was successfully transferred with 5-8x10^7 immune lymph node and spleen cells into naive mice. CD4^+ T cells were responsible for this sensitivity, since 1x10^7 CD4^+ cells alone induced a high level of sensitivity reaction and the addition of other lymphocyte populations did not enhance the reaction. Culture supernatants from immune lymph node cells contained a higher level of IL-4 and a lower level of interferon-g than those from naive mice. Finally, the skin of AQ-photochallenged site exhibited high expression of CCL24/eotaxin-2, a chemokine for eosinophils. It is suggested that eosinophilic drug photoallergy is medated by sensitized Th2 cells and locally produced eosinophil-attracting chemokines. This model is useful for exploring the mechanism of eosinophil-infiltrating photosensitivity.

我们建立了一个小鼠模型的嗜酸性粒细胞浸润型药物光变态反应，通过使用afloqualone（AQ），一个代表性的光敏药物。AKR/J小鼠通过腹膜内注射阿氟喹酮溶液和用UVA照射剃毛的腹部来致敏。将该致敏程序重复2-12次（每周两次），并且在最后一次免疫后3天，通过皮下注射法攻击小鼠。注射AQ溶液并用UVA照射相同部位。接受超过10次致敏的小鼠在激发部位表现出大量嗜酸性粒细胞和淋巴细胞浸润。这种反应是AQ光抗原特异性的，AKR/J小鼠是这种敏感性的高应答品系。用5-8x10^7免疫淋巴结和脾细胞成功地将敏感性转移到幼稚小鼠中。CD 4 ^+ T细胞是这种敏感性的原因，因为1 × 10^7个CD 4 ^+细胞单独诱导了高水平的敏感性反应，而加入其他淋巴细胞群并不能增强反应。免疫淋巴结细胞培养上清中IL-4水平较高，干扰素-g水平较低。最后，AQ-photocharged网站的皮肤表现出高表达的CCL 24/嗜酸性粒细胞趋化因子-2，嗜酸性粒细胞。这表明，嗜酸性药物光过敏介导的致敏的Th 2细胞和本地产生的嗜酸性粒细胞吸引趋化因子。该模型可用于探讨嗜酸性粒细胞浸润光敏性的机制。

项目成果

Induction of keratinocyte apoptosis by photosensitizingchemicals plus UVA.

通过光敏化学物质加 UVA 诱导角质形成细胞凋亡。

• 发表时间: 2007
• 期刊: J Dermatol Sci 45
• 作者: 宮地 良樹;他;川上民裕;Tokura Y;Mon T;Shimauchi T;Tokura Y;Kurita M;Kabashima K;Kabashima K;Kabashima K;Hino R;Atarashi K;Nishio D;戸倉 新樹;Kurita M
• 通讯作者: Kurita M

Solar urticaria as a manifestation of Churg-Strauss syndrome

日光性荨麻疹是 Churg-Strauss 综合征的一种表现

• 发表时间: 2006
• 期刊: Clin Exp Dermatol 32
• 作者: 宮地 良樹;他;川上民裕;Tokura Y;Mon T;Shimauchi T;Tokura Y;Kurita M;Kabashima K;Kabashima K;Kabashima K;Hino R;Atarashi K;Nishio D;戸倉 新樹;Kurita M;Kabashima K;Kabashima K;Kabashima K;Hino R;Atarashi K;Nishio D;Kurita M;Hino R;Nishio D;Schroder JM;Kabashima K;Imai S;Shimauchi T
• 通讯作者: Shimauchi T

目で見るアレルギー性皮膚疾患

视觉过敏性皮肤病

• 发表时间: 2007
• 作者: Hirose S.;et al;森田 明理
• 通讯作者: 森田 明理

Establishment of murine model of allergic photocontact dermatitis to ketoprofen and characterization of pathogenic T cells

• DOI: 10.1016/j.jdermsci.2005.08.006
• 发表时间: 2006-02-01
• 期刊: JOURNAL OF DERMATOLOGICAL SCIENCE
• 影响因子: 4.6
• 作者: Imai, S;Atarashi, K;Tokura, Y
• 通讯作者: Tokura, Y

Who is really in control of skin immunity under physiological circumstances – lymphocytes, dendritic cells or keratinocytes?

• DOI: 10.1111/j.1600-0625.2006.00506_1.x
• 发表时间: 2006-11
• 期刊: Experimental Dermatology
• 影响因子: 3.6
• 作者: R. Paus;J. Schröder;K. Reich;K. Kabashima;F. Liu;N. Romani;M. Metz;A. Kerstan;P. H. A. Lee-P.-H.-A.-L