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

Andreas Willerslev-Olsen, Lise Mette Rahbek Gjerdrum, Lise M Lindahl, Terkild B Buus, Emil M H Pallesen, Maria Gluud, Michael Bzorek, Boye S Nielsen, Maria R Kamstrup, Anne Hald Rittig, Charlotte M Bonefeld, Thorbjørn Krejsgaard, Carsten Geisler, Sergei B Koralov, Thomas Litman, Jurgen C Becker, Anders Woetmann, Lars Iversen, Niels Odum*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)2449-2458
Antal sider10
TidsskriftJournal of Investigative Dermatology
Vol/bind141
Udgave nummer10
Tidlig onlinedato20 apr. 2021
DOI
StatusUdgivet - okt. 2021

Bibliografisk note

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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