Plasmacytoid Dendritic Cells: A New Cutaneous Dendritic Cell Subset with Distinct Role in Inflammatory Skin Diseases

Abstract

Epidermal dendritic cells found in inflamed skin include Langerhans cells and the recently identified population of inflammatory dendritic epidermal cells. Another subset of dendritic cells in humans is the plasmacytoid dendritic cell in peripheral blood, which is characterized by the production of large amounts of type I interferon (interferon-alpha and interferon-beta) upon viral infection. We hypothesized that plasmacytoid dendritic cells might be involved in anti-viral defense mechanisms of the skin. Here we investigated plasmacytoid dendritic cells, inflammatory dendritic epidermal cells, and Langerhans cells in epidermal single cell suspensions of normal looking skin from healthy volunteers and of lesional skin from patients with different inflammatory skin diseases. Langerhans cells were found in normal and in inflamed skin samples. In normal skin, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells were low or absent. Lesional skin samples from patients with psoriasis vulgaris and contact dermatitis contained relatively high numbers of both inflammatory dendritic epidermal cells and plasmacytoid dendritic cells. In contrast, many inflammatory dendritic epidermal cells but only very few plasmacytoid dendritic cells could be detected in atopic dermatitis lesions. Lupus erythematosus was characterized by high numbers of plasmacytoid dendritic cells but low numbers of inflammatory dendritic epidermal cells. These results demonstrate that in addition to resident Langerhans cells, plasmacytoid dendritic cells and inflammatory dendritic epidermal cells are selectively recruited to the skin lesions depending on the type of skin disease. The lack of plasmacytoid dendritic cells in atopic dermatitis may predispose atopic dermatitis patients to viral infections such as eczema herpeticum, a secondary infection of atopic dermatitis lesions with herpes simplex virus. The composition of dendritic cell subsets may help to clarify the etiology of inflammatory skin diseases and forms the basis for therapeutic intervention with selective microbial molecules such as immunostimulatory CpG oligonucleotides.

The type I interferon system in systemic lupus erythematosus

“…Gene expression profiles of minor salivary gland biopsy specimens also show an up-regulation of type I IFNregulated genes (105). Skin biopsy specimens obtained from patients with psoriasis display increased expression of mRNA for both IFN␣ and IFN-induced proteins as well as an infiltration of NIPCs/PDCs (46,106). Furthermore, an essential role for NIPCs/PDCs and IFN␣ in the development of psoriatic lesions was recently demonstrated in a xenograft model of human psoriasis (107).…”

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

“…Extracellular HMGB1 mediates endotoxin lethality and inflammation [32,[42][43][44][45][46]. These findings suggest that HMGB1 may be involved in regulating the function of PDC, which have been implicated in the pathogenesis of cancer [47,48] and chronic inflammatory conditions like systemic lupus erythematosus and allergy [49][50][51].…”

Antimicrobial Peptides, Skin Infections, and Atopic Dermatitis

“…118 The reason for this depletion is by dose-dependent plasmacytoid dendritic cell apoptosis induction caused by IL-4, and potentiated by IL-10. 119…”