1. ¹Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA
2. ²Hospital Program Direction, Translational Immunomonitoring Resource Center, The Rockefeller University, New York, New York, USA

Correspondence: Michelle A. Lowes, Rockefeller University, Investigational Dermatology, 1230 York Avenue, New York, NY 10065, USA. E-mail: lowesm@rockefeller.edu

Received 20 February 2008; Revised 1 April 2008; Accepted 10 May 2008; Published online 17 July 2008.

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⁺-blood dendritic cell antigen (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. Although BDCA-1⁺ DCs are not increased in number in psoriatic lesional skin compared with 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 allogeneic mixed leukocyte reaction. Both BDCA-1⁺ and BDCA-1^- myeloid dermal DC populations induced T-cell proliferation, and polarized T cells to become T helper 1 (Th1) and T helper 17 (Th17) cells. In addition, psoriatic dermal DCs induced a population of activated T cells that simultaneously produced IL-17 and IFN-, 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⁺IFN-⁺ 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.