Regulatory T cells coNTROL VEGF-dependent skin inflammation

Abstract

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 (CD4CD25CD127low) 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 CD4CD25 T cells were transferred to naive K14VEGF transgenic mice before TPA challenge. CD4CD25 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.