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.
Teige
Ingrid
I
Department of Pharmacology, Section of Dermatology, Discovery, LEO Pharma A/S, Ballerup, Denmark.
Hvid
Henning
H
Svensson
Lars
L
Kvist
Peter Helding
PH
Kemp
Kåre
K
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D007249:Inflammation; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D012867:Skin / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D013755:Tetradecanoylphorbol Acetate