Psoriasis Is Characterized by Accumulation of Immunostimulatory and Th1/Th17 Cell-Polarizing Myeloid Dendritic Cells

Abstract

Myeloid dermal dendritic cells (DCs) accumulate in chronically inflamed tissues such as psoriasis. The importance of these cells for psoriasis pathogenesis is suggested by comparative T cell and DC cell counts, where DCs outnumber T cells. We have previously identified CD11c+BDCA-1+ cells as the main resident dermal DC population found in normal skin. We now show that psoriatic lesional skin has two populations of dermal DCs: 1) CD11c+BDCA-1+ cells which are phenotypically similar to those contained in normal skin, and 2) CD11c+BDCA-1− cells which are phenotypically immature and produce inflammatory cytokines. While BDCA-1+ DCs are not increased in number in psoriatic lesional skin compared to normal skin, BDCA-1− DCs are increased 30-fold. For functional studies, we FACS-sorted psoriatic dermal single cell suspensions to isolate these two cutaneous DC populations, and cultured them as stimulators in an allo-MLR. Both BDCA-1+ and BDCA-1− myeloid dermal DC populations induced T cell proliferation, and polarized T cells to become Th1 and Th17 cells. In addition, psoriatic dermal DCs induced a population of activated T cells that simultaneously produced IL-17 and IFN-γ, which was not induced by normal skin dermal DCs. As psoriasis is believed to be a mixed Th17/Th1 disease, it is possible that induction of these IL-17+IFNγ+ cells is pathogenic. These cytokines, the T cells that produce them, and the inducing inflammatory DCs may all be important new therapeutic targets in psoriasis.