Identification of a novel pro-inflammatory human skin-homing V gamma 9V delta 2 T cell subset and its role in the pathogenesis of psoriasis

gd T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human gd cells in cutaneous homeostasis and pathology is characterized poorly. In this study, we show in vivo evidence that human blood contains a distinct subset of proinflammatory cutaneous lymphocyte Ag and CCR6-positive V g 9V d 2 T cells, which is rapidly recruited into perturbed human skin. V g 9V d 2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF- a – and IFN- g –dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating V g 9V d 2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating V g 9V d 2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of V g 9V d 2 T cells in psoriatic skin, these data indicate redistribution of V g 9V d 2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory gd T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease. The Journal of Immunology , 2011, 187: 2783–2793. and repeated measure one-way ANOVA was used for more than two matched groups. To compare not normally distributed samples, we used Mann–Whitney U test to compare two groups and Kruskal–Wallis test for comparison of three groups. As a nonparametric test for two paired groups, we used Wilcoxon matched pair test. Pearson correlation was used to correlate clinical variables and percentage/absolute numbers of gd T cells, whereas one-way exponential decay was applied for calculation of R 2 . For all statistical tests, we con- sidered p values , 0.05 to be statistically significant. Results are expressed as mean 6 SEM.