Epidermal CCR6+ γδ T Cells Are Major Producers of IL-22 and IL-17 in a Murine Model of Psoriasiform Dermatitis

Abstract

Cytokine components of Th17 pathway play vital roles in human psoriasis. Although much is known about TCR αβ T cells in psoriasis, the role of unconventional T cells, including γδ T cells, is unclear. In this study, using an IL-23 skin injection model of psoriasiform dermatitis in mice, we demonstrate that IL-22, IL-17A, and the IL-23R were highly enriched in a population of CCR6(+), TCR γδ-low expressing (GDL) T cells that accumulated in the epidermis after IL-23 injections. GDL cells were distinct from resident TCR γδ-high, Vγ3(+),CCR6(-) T cells in the epidermis that did not change appreciably in numbers following IL-23 injection. Large numbers of CCR6(+) cells were detected at or above the level of the epidermal basement membrane by confocal microscopy 5 d after repeated IL-23 injections at the same time GDL cells increased in numbers in the epidermis. TCR δ-deficient mice (lacking γδ T cells) exhibited decreased ear swelling and downregulated expression of IL-22 and IL-17A in the epidermis following IL-23 injection. Our data suggest that a subset of γδ T cells play a critical role in IL-23-mediated psoriasiform dermatitis.