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/ß-Producing Cells) Accumulate in Cutaneous Lupus Erythematosus Lesions
From the Laboratory for Immunohistochemistry and Immunopathology, Institute and Department of Pathology, University of Oslo, Rikshospitalet, Oslo, Norway
Plasmacytoid dendritic cell (P-DC) precursors in peripheral blood
produce large amounts of interferon (IFN)-
/ß when triggered by
viruses. However, when incubated with interleukin-3 and CD40
ligand, the same precursors differentiate into mature DCs that
stimulate naïve CD4+ T cells to produce Th2
cytokines. We recently reported that P-DCs accumulate in nasal mucosa
of experimentally induced allergic rhinitis, supporting a role
for this DC subset in Th2-dominated inflammation. Here we examined
whether P-DCs accumulate in cutaneous lesions of lupus erythematosus
(LE), a disorder associated with increased IFN-/ß
production. Our results showed that P-DCs were present in 14 out of 15
tissue specimens of cutaneous LE lesions, but not in normal
skin. Importantly, the density of P-DCs in affected skin
correlated well (rs = 0.79,P < 0.0005) with the high number of cells
expressing the IFN-/ß-inducible protein MxA, suggesting
that P-DCs produce IFN-/ß locally. Accumulation of P-DCs coincided
also with the expression of L-selectin ligand peripheral
lymph node addressin on dermal vascular endothelium, adding
further support to the notion that these adhesion molecules are
important in P-DC extravasation to peripheral tissue sites.
Together, our findings suggested that P-DCs are an important
source of IFN-/ß in cutaneous LE lesions and may therefore be of
pathogenic importance.
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P. Brawand, D. R. Fitzpatrick, B. W. Greenfield, K. Brasel, C. R. Maliszewski, and T. De Smedt Murine Plasmacytoid Pre-Dendritic Cells Generated from Flt3 Ligand-Supplemented Bone Marrow Cultures Are Immature APCs J. Immunol., December 15, 2002; 169(12): 6711 - 6719. [Abstract] [Full Text] [PDF]
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L. Ronnblom and G. V. Alm A Pivotal Role for the Natural Interferon {alpha}-producing Cells (Plasmacytoid Dendritic Cells) in the Pathogenesis of Lupus J. Exp. Med., December 17, 2001; 194(12): F59 - F64. [Full Text] [PDF]
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A. Dzionek, Y. Sohma, J. Nagafune, M. Cella, M. Colonna, F. Facchetti, G. Gunther, I. Johnston, A. Lanzavecchia, T. Nagasaka, et al. BDCA-2, a Novel Plasmacytoid Dendritic Cell-specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon {alpha}/{beta} Induction J. Exp. Med., December 17, 2001; 194(12): 1823 - 1834. [Abstract] [Full Text] [PDF]
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P. Bjorck Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice Blood, December 15, 2001; 98(13): 3520 - 3526. [Abstract] [Full Text] [PDF]
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 P. Blanco, A. K. Palucka, M. Gill, V. Pascual, and J. Banchereau Induction of Dendritic Cell Differentiation by IFN-alpha in Systemic Lupus Erythematosus Science, November 16, 2001; 294(5546): 1540 - 1543. [Abstract] [Full Text] [PDF]
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