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患有皮炎的白细胞介素-7转基因小鼠表现出的免疫异常。

Immunologic abnormalities exhibited in IL-7 transgenic mice with dermatitis.

作者信息

Uehira M, Matsuda H, Nakamura A, Nishimoto H

机构信息

Shionogi Institute for Medical Science, Osaka, Japan.

出版信息

J Invest Dermatol. 1998 May;110(5):740-5. doi: 10.1046/j.1523-1747.1998.00179.x.

DOI:10.1046/j.1523-1747.1998.00179.x
PMID:9579538
Abstract

Interleukin (IL)-7 transgenic mice, which we established previously, developed severe dermatitis characterized by massive infiltration of gammadelta T cells in the dermal lesion. To fully understand the pathology of this intriguing skin disease, we examined several immunologic features of dermis infiltrating lymphocytes from the lesional skin of IL-7 transgenic mice. We observed a moderate response to mitogens, a poor response to alloantigens, and the absence of cytotoxic activities to several tumor cell lines and skin derived cells regardless of the presence of IL-2 or IL-7. On the other hand, dermis infiltrating lymphocytes could proliferate with exogenous IL-2 and IL-7. Moreover, reverse transcriptase polymerase chain reaction and fluorescence activated cell sorter analysis revealed that dermis infiltrating lymphocytes expressed various cytokines including IL-4 and IL-7, and several activation markers for T cells (CD44, CD69, IL-2R alpha), in addition to IL-7R alpha. In the sera of the affected mice, hyper epsilon-globulinemia was observed. These findings suggested that dermis infiltrating lymphocytes proliferated in an activated state in the skin lesion in an autocrine and/or paracrine manner and produced Th2 type cytokines that might evoke immunologic abnormalities. This study and previous findings suggest that IL-7 transgenic mouse with dermatitis offer the potential of serving as a useful tool for investigating the immunologic role of cutaneous gammadelta T cells, especially their participation in IgE production in vivo.

摘要

我们先前构建的白细胞介素(IL)-7转基因小鼠出现了严重的皮炎,其特征为皮肤病变处有大量γδT细胞浸润。为了全面了解这种有趣皮肤病的病理,我们检测了来自IL-7转基因小鼠病变皮肤真皮浸润淋巴细胞的几种免疫学特征。我们观察到这些细胞对丝裂原的反应适度,对同种异体抗原的反应较差,并且无论是否存在IL-2或IL-7,对几种肿瘤细胞系和皮肤来源细胞均无细胞毒性活性。另一方面,真皮浸润淋巴细胞可通过外源性IL-2和IL-7进行增殖。此外,逆转录聚合酶链反应和荧光激活细胞分选分析显示,真皮浸润淋巴细胞除了表达IL-7Rα外,还表达包括IL-4和IL-7在内的多种细胞因子,以及几种T细胞激活标志物(CD44、CD69、IL-2Rα)。在患病小鼠的血清中,观察到高ε球蛋白血症。这些发现表明,真皮浸润淋巴细胞在皮肤病变中以自分泌和/或旁分泌方式在激活状态下增殖,并产生可能引发免疫异常的Th2型细胞因子。本研究和先前的发现表明,患有皮炎的IL-7转基因小鼠有可能成为研究皮肤γδT细胞免疫作用,特别是它们在体内参与IgE产生的有用工具。

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Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.对21000例病例和95000例对照进行的多血统全基因组关联研究确定了特应性皮炎的新风险位点。
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