Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells.

Lisa C. Zaba, Judilyn Fuentes-Duculan, Narat John Eungdamrong, Maria Veronica Abello, Inna Novitskaya, Katherine C. Pierson, Juana Gonzalez, James G. Krueger, Michelle A. Lowes

Research output: Contribution to journalArticle

295 Scopus citations

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-gamma, 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-gamma(+) 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.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalThe Journal of investigative dermatology
Volume129
Issue number1
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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