Interferon-α stimulates TRAIL expression in human keratinocytes and peripheral blood mononuclear cells: implications for the pathogenesis of cutaneous lupus erythematosus

Background The tumour necrosis factor-related apoptosis-inducing ligand TRAIL has been shown to participate in the pathogenesis of systemic lupus erythematosus (SLE). The accumulation of apoptotic cell debris has been hypothesized to induce this autoimmune inflammation, and TRAIL may trigger this programmed cell death. Furthermore, TRAIL is among the interferon (IFN)-regulated genes which are typically expressed in the peripheral blood of patients with acute SLE. Objectives As an inappropriate activation of the type I IFN system plays an important role in both SLE and cutaneous lupus erythematosus (CLE) subsets, we hypothesized that TRAIL might also participate in the pathogenesis of CLE. Methods Immunohistochemistry and immunofluorescence analyses were used to identify and localize TRAIL-expressing cells in CLE skin specimens. TRAIL expression in peripheral blood mononuclear cells (PBMC) isolated from patients with CLE was measured by flow cytometry. The impact of IFN-alpha treatment on TRAIL expression by keratinocytes and PBMC was evaluated by reverse transcription-polymerase chain reaction and flow cytometry. Results Keratinocytes are beside CD11c+ and BDCA2+ dendritic cells the major TRAIL-expressing cells in CLE lesions. TRAIL is upregulated on the surface of circulating CD11c+ PBMC isolated from patients with CLE. Treatment of keratinocytes and PBMC with recombinant IFN-alpha strongly enhances TRAIL expression by these cells. The proapoptotic TRAIL receptor R1 is expressed by keratinocytes in CLE skin lesions. Conclusions TRAIL is strongly expressed in the skin and the blood of patients with CLE and may trigger the apoptotic death of kerationcytes in CLE via the TRAIL receptor R1. An IFN-alpha-induced TRAIL expression may in this way participate in the pathogenesis of CLE.