Psoriasis is a common inflammatory skin disease with limited treatment options that is characterized by a complex interplay between keratinocytes, immune cells, and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression and play critical roles in many human diseases. A number of miRNAs have been described to be up-regulated in psoriasis, but their causal contribution to disease development has not been demonstrated. We confirm that miR-21 expression is increased in epidermal lesions of patients with psoriasis and that this leads to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3) expression and activation of TACE (tumor necrosis factor-α-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived skin samples and mouse models of psoriasis, we demonstrate that increased miR-21 may be a consequence of impaired transcriptional activity of Jun/activating protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21 by locked nucleic acid (LNA)-modified anti-miR-21 compounds ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model. Targeting miR-21 may represent a potential therapeutic option for the treatment of psoriasis.
Herpes zoster (HZ) occurs with an increased incidence in immunosuppressed patients, in whom it frequently displays atypical clinical presentations. Herpetic syringitis, the involvement of the eccrine epithelium by herpes virus infection, is an infrequently described histologic pattern that has been rarely and almost exclusively reported in HIV-infected patients. We report the case of a woman with Burkitt lymphoma who developed 2 nodular, asymptomatic lesions while receiving treatment with chemotherapy and radiotherapy for her hematological disease. Histology showed viropathic changes in the epithelium of eccrine glands not in the epidermis. PCR was positive for varicella-zoster virus (VZV). Nodular herpes zoster seems to be an exceptional clinical presentation. We report another such case which is, as far as we know, the first report of herpetic syringitis with no concomitant epidermal involvement.
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