Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions

Am J Pathol. 2001 Jul;159(1):237-43. doi: 10.1016/s0002-9440(10)61689-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Endothelium, Vascular / metabolism
  • GTP-Binding Proteins*
  • Humans
  • Interferon-alpha / biosynthesis
  • Interferon-beta / biosynthesis
  • Lupus Erythematosus, Discoid / metabolism
  • Lupus Erythematosus, Discoid / pathology
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / pathology*
  • Membrane Proteins
  • Myxovirus Resistance Proteins
  • Organ Culture Techniques
  • Proteins / metabolism
  • Skin / blood supply
  • Skin / metabolism
  • Skin / pathology*
  • Stem Cells / metabolism
  • Stem Cells / pathology*

Substances

  • Antigens, Surface
  • Interferon-alpha
  • L-selectin counter-receptors
  • MX1 protein, human
  • Membrane Proteins
  • Myxovirus Resistance Proteins
  • Proteins
  • Interferon-beta
  • GTP-Binding Proteins