Identification of a Novel Proinflammatory Human Skin-Homing V gamma 9V delta 2 T Cell Subset with a Potential Role in Psoriasis

gamma delta T cells mediate rapid tissue responses in murine skin and participate in cutaneous immune regulation including protection against cancer. The role of human gamma delta 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 gamma 9V delta 2 T cells, which is rapidly recruited into perturbed human skin. V gamma 9V delta 2 T cells produced an array of proinflammatory mediators including IL-17A and activated keratinocytes in a TNF- alpha - and IFN- gamma -dependent manner. Examination of the common inflammatory skin disease psoriasis revealed a striking reduction of circulating V gamma 9V delta 2 T cells in psoriasis patients compared with healthy controls and atopic dermatitis patients. Decreased numbers of circulating V gamma 9V delta 2 T cells normalized after successful treatment with psoriasis-targeted therapy. Taken together with the increased presence of V gamma 9V delta 2 T cells in psoriatic skin, these data indicate redistribution of V gamma 9V delta 2 T cells from the blood to the skin compartment in psoriasis. In summary, we report a novel human proinflammatory gamma delta T cell involved in skin immune surveillance with immediate response characteristics and with potential clinical relevance in inflammatory skin disease.