Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis

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Abstract

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.

Authors

Wanhong Ding, Stefan Beissert, Liang Deng, Edward Miranda, Christopher Cassetty, Kristina Seiffert, Kristina L. Campton, Zhengmin Yan, George F. Murphy, Jeffrey A. Bluestone, Richard D. Granstein