Regulatory T Cells Control VEGF-Dependent Skin Inflammation

Transgenic mice expressing vascular endothelial growth factor (VEGF) under the keratin 14 promoter have been described to develop a psoriasis-like inflammation characterized by increased angiogenesis, acanthosis, and immune cell infiltration. We have recently shown that applying 12-O-tetradecanoylphorbol-13-acetate (TPA) in these mice induces a severe and long-lasting skin inflammation with a Th17 cell signature. Here, we aimed to study the function of CD4+ T cells using this model. Lymphocytes isolated from inflamed ears showed a significantly higher number of activated T cells, in contrast to the primarily naive lymphocytes isolated from blood. In addition, there was an increase in regulatory T cells (CD4+CD25+CD127−/low) within the skin. To clarify the function of CD4+ cells, we depleted CD4+ T cells using antibody. CD4 depletion resulted in augmented ear thickness and proinflammatory cytokine levels, indicating that CD4+ T cells have a suppressive rather than a proinflammatory function in this model. Subsequently, sorted regulatory CD4+CD25+ T cells were transferred to naive K14/VEGF transgenic mice before TPA challenge. CD4+CD25+ T-cell transfer significantly reduced ear thickness and proinflammatory cytokine production compared to controls. This shows that a persistent skin inflammation with similarities to psoriasis can be controlled by a single injection of few regulatory T cells.