Plasmacytoid dendritic cells are present in cutaneous dermatomyositis lesions in a pattern distinct from lupus erythematosus

Abstract

Background: Plasmacytoid dendritic cells (PDCs) are CD123‐positive dendritic cells (DCs) capable of producing interferon‐α (IFN). They are thought to play a role in anti‐viral immunity and the pathogenesis of lupus erythematosus (LE). Given the histologic similarities between LE and dermatomyositis (DM), we evaluated the presence and distribution of PDCs in lesional skin of both diseases.Methods: Twenty‐eight biopsies of DM and 27 biopsies of LE were labeled with antibodies to CD123 to identify PDCs. The presence and relative distribution of CD123+ cells was recorded.Results: PDCs are present in LE and DM, albeit in greater numbers in LE lesions. Interestingly, PDCs are preferentially located in the epidermis of DM, and are primarily located in the dermis of LE.Conclusions: Skin lesions of DM contain PDCs. Because PDCs are thought to participate in the pathogenesis of LE, this finding suggests that they may play a role in DM as well. The preferential epidermal localization of PDCs in DM suggests that their contribution to disease pathogenesis or maintenance in DM may be distinct from LE. Finally, although not pathognomonic, the different patterns of PDC localization in LE and DM may prove a helpful criterion for distinguishing between these two entities histologically.

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

“…These findings support a crucial role for type I interferons in pathological features of DM [56]. One of the well-known mechanism that induces type I IFN production is the trigger of toll-like receptors (TLR7 and 9) in plasmacytoid dendritic cells (pDCs), specialized in the production of type I IFN, which resulted abundant both in the skin lesions of SLE patients and in the affected muscle cells of DM patients [48,57].…”

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

“…3,8,[14][15][16][17][18][19][20][21][23][24][25][26][27][28] We, therefore, hypothesized that EMP could trigger PDC maturation and that such an interaction could contribute to the above mentioned inflammatory disorders. Here, we demonstrate that EMP can indeed induce PDC maturation, as shown by co-stimulatory molecule upregulation, inflammatory cytokine secretion, and by allogeneic naive CD4 + T-cell proliferation.…”

“…Increased levels of EMP have been reported in a variety of pathological situations including thrombosis, 3,8 atherosclerosis, 14 renal failure, 15,16 diabetes, 17 graftversus-host disease after hematopoietic cell transplantation 18,19 and systemic lupus erythematosus. 1,20,21 These data emphasize the link between endothelial damage, the release of EMP and the modulation of inflammatory and/or immune responses.…”

Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

“…Recently published studies have documented the cutaneous accumulation of type I IFN producing PDC either in (Blomberg et al 2001;Farkas et al 2001;Wenzel et al 2007a;McNiff and Kaplan 2008) a limited number of LE patients. Taking advantage on the availability of reagents recognizing PDC on fixed tissue, we studied a cohort of 74 patients and confirmed that cutaneous PDC infiltration represents the hallmark of LE.…”