Staphylococcus aureus Induces Signal Transducer and Activator of Transcription 5‒Dependent miR-155 Expression in Cutaneous T-Cell Lymphoma

• Published in: Journal of investigative dermatology Vol. 141; no. 10; pp. 2449 - 2458
• Main Authors: Willerslev-Olsen, Andreas, Gjerdrum, Lise Mette Rahbek, Lindahl, Lise M., Buus, Terkild B., Pallesen, Emil M.H., Gluud, Maria, Bzorek, Michael, Nielsen, Boye S., Kamstrup, Maria R., Rittig, Anne Hald, Bonefeld, Charlotte M., Krejsgaard, Thorbjørn, Geisler, Carsten, Koralov, Sergei B., Litman, Thomas, Becker, Jurgen C., Woetmann, Anders, Iversen, Lars, Odum, Niels
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021
• Subjects: SS; miRNA; SE; STAT; pY-STAT5; CTCL
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2021.01.038

Staphylococcal enterotoxins are believed to fuel disease activity in cutaneous T-cell lymphoma. Recent data support this by showing that antibiotics inhibit malignant T cells in skin lesions in mycosis fungoides and Sézary syndrome, the most common forms of cutaneous T-cell lymphoma. Yet, it remains incompletely characterized how staphylococcal enterotoxins fuel disease activity. In this study, we show that staphylococcal enterotoxins induce the expression of the oncogenic microRNA miR-155 in primary malignant T cells. Thus, staphylococcal enterotoxins and Staphyloccocus aureus isolates from lesional skin of patients induce miR-155 expression at least partly through the IL-2Rg‒Jak‒signal transducer and activator of transcription 5 pathway, and the effect is augmented by the presence of nonmalignant T cells. Importantly, mycosis fungoides lesions harbor S. aureus, express Y-phosphorylated signal transducer and activator of transcription 5, and display enhanced miR-155 expression, when compared with nonlesional and healthy skin. Preliminary data show that aggressive antibiotic therapy is associated with decreased Y-phosphorylated signal transducer and activator of transcription 5 and miR-155 expression in lesional skin in two patients with Sézary syndrome. In conclusion, we show that S. aureus and its enterotoxins induce enhanced expression of oncogenic miR-155, providing mechanistic insight into the role of S. aureus in cutaneous T-cell lymphoma. Our findings support that environmental stimuli such as bacteria can fuel disease progression in cutaneous T-cell lymphoma.