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

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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
JournalJournal of Investigative Dermatology
Volume129
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

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Th17 Cells
Myeloid Cells
Psoriasis
Langerhans Cells
Dendritic Cells
Blood Cells
Antigens
T-cells
T-Lymphocytes
Blood
Skin
Interleukin-17
Population
Cytokines
Mixed Lymphocyte Culture Test
Suspensions
Cell Count
Cell Proliferation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Zaba, L. C., Fuentes-Duculan, J., Eungdamrong, N. J., Abello, M. V., Novitskaya, I., Pierson, K. C., ... Lowes, M. A. (2009). Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. Journal of Investigative Dermatology, 129(1), 79-88. https://doi.org/10.1038/jid.2008.194

Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. / Zaba, Lisa C.; Fuentes-Duculan, Judilyn; Eungdamrong, Narat John; Abello, Maria Veronica; Novitskaya, Inna; Pierson, Katherine C.; Gonzalez, Juana; Krueger, James G.; Lowes, Michelle A.

In: Journal of Investigative Dermatology, Vol. 129, No. 1, 01.2009, p. 79-88.

Research output: Contribution to journalArticle

Zaba, LC, Fuentes-Duculan, J, Eungdamrong, NJ, Abello, MV, Novitskaya, I, Pierson, KC, Gonzalez, J, Krueger, JG & Lowes, MA 2009, 'Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells.', Journal of Investigative Dermatology, vol. 129, no. 1, pp. 79-88. https://doi.org/10.1038/jid.2008.194
Zaba, Lisa C. ; Fuentes-Duculan, Judilyn ; Eungdamrong, Narat John ; Abello, Maria Veronica ; Novitskaya, Inna ; Pierson, Katherine C. ; Gonzalez, Juana ; Krueger, James G. ; Lowes, Michelle A. / Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 1. pp. 79-88.
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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.",
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