Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions.
Plasmacytoid dendritic cell (P-DC) precursors in peripheral blood produce large amounts of interferon (IFN)-alpha/beta 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-alpha/beta 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 (r(s) = 0.79,P < 0.0005) with the high number of cells expressing the IFN-alpha/beta-inducible protein MxA, suggesting that P-DCs produce IFN-alpha/beta 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-alpha/beta in cutaneous LE lesions and may therefore be of pathogenic importance.
Farkas
L
L
Laboratory for Immunohistochemistry and Immunopathology, University of Oslo, Rikshospitalet, Oslo, Norway. lorant.farkas@labmed.uio.no
Beiske
K
K
Lund-Johansen
F
F
Brandtzaeg
P
P
Jahnsen
F L
FL
D000954:Antigens, Surface / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism; D019204:GTP-Binding Proteins; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008179:Lupus Erythematosus, Discoid / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D009924:Organ Culture Techniques; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
D000954:Antigens, Surface; D016898:Interferon-alpha; C069886:L-selectin counter-receptors; C579071:MX1 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D016899:Interferon-beta; D019204:GTP-Binding Proteins