Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis.
Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis.
复制标题
DOI：
10.1172/jci15722
复制
发表时间：
2003-06
期刊：
影响因子：
--
通讯作者：
W. Ding;S. Beissert;L. Deng;E. Miranda;Christopher T Cassetty;K. Seiffert;K. Campton;Zhengming Yan;G. Murphy;J. Bluestone;R. Granstein
中科院分区：
文献类型：
--
作者：
W. Ding;S. Beissert;L. Deng;E. Miranda;Christopher T Cassetty;K. Seiffert;K. Campton;Zhengming Yan;G. Murphy;J. Bluestone;R. Granstein
IL-10是一种多效性细胞因子，可抑制多种免疫参数，包括Th1细胞介导的免疫反应、抗原提呈和抗原特异性T细胞增殖。最近的数据表明，IL-10是UVB辐射(280-320 nm)诱导的细胞免疫抑制的中介物。为了研究IL-10对皮肤免疫系统的影响，我们设计了在表皮中高表达病毒IL-10(VIL-10)的转基因小鼠。VIL-10转基因小鼠皮肤涂覆半抗原后，局部淋巴结中I-A(+)表皮和真皮细胞数量减少，I-A(+)半抗原阳性细胞减少。I-A(+)表皮细胞CD80、CD86表达降低。VIL-10转基因小鼠在攻击时对异体细胞表现出较小的迟发性超敏反应，但对表面应用的半抗原具有正常的接触性超敏反应。来自VIL-10转基因小鼠的新鲜表皮细胞刺激同种异体T细胞增殖的能力降低，脾细胞也是如此。此外，在VIL-10小鼠中，长期暴露于UVB辐射导致的皮肤肿瘤比WT对照组小鼠更少，VIL-10转基因小鼠对YAC-1靶点的脾NK细胞活性增加。这些发现支持IL-10是皮肤免疫功能的重要调节因子的概念。
IL-10 is a pleiotropic cytokine that inhibits several immune parameters, including Th1 cell-mediated immune responses, antigen presentation, and antigen-specific T cell proliferation. Recent data implicate IL-10 as a mediator of suppression of cell-mediated immunity induced by exposure to UVB radiation (280-320 nm). To investigate the effects of IL-10 on the cutaneous immune system, we engineered transgenic mice that overexpress viral IL-10 (vIL-10) in the epidermis. vIL-10 transgenic mice demonstrated a reduced number of I-A(+) epidermal and dermal cells and fewer I-A(+) hapten-bearing cells in regional lymph nodes after hapten painting of the skin. Reduced CD80 and CD86 expression by I-A(+) epidermal cells was also observed. vIL-10 transgenic mice demonstrated a smaller delayed-type hypersensitivity response to allogeneic cells upon challenge but had normal contact hypersensitivity to an epicutaneously applied hapten. Fresh epidermal cells from vIL-10 transgenic mice showed a decreased ability to stimulate allogeneic T cell proliferation, as did splenocytes. Additionally, chronic exposure of mice to UVB radiation led to the development of fewer skin tumors in vIL-10 mice than in WT controls, and vIL-10 transgenic mice had increased splenic NK cell activity against YAC-1targets. These findings support the concept that IL-10 is an important regulator of cutaneous immune function.