Forskning ved Københavns Universitet - Københavns Universitet


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

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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.

TidsskriftJournal of Investigative Dermatology
StatusAccepteret/In press - 2021

Bibliografisk note

Funding Information:
JCB is receiving speaker’s bureau honoraria from Amgen, Pfizer, Merck Serono, Recordati, and Sanofi and is a paid consultant/advisory board member for Boehringer Ingelheim, eTheRNA Immunotherapies NV, InProTher, Merck Serono, Pfizer, 4SC, and Sanofi. His group receives research grants from Bristol-Myers Squibb, Merck Serono, HTG, IQVIA, and Alcedis. NO has an advisory consultant honorarium from Micreos human Health B.V and Almirall. LMRG receives funding from NanoString Technologies. TL is funded by LEO Pharma. The remaining authors state no conflict of interest.

Funding Information:
This research was funded by LEO Foundation , The Danish Cancer Society (Kræftens Bekæmpelse), the Fight Cancer Program (Knæk Cancer), Novo Nordisk Research Foundation , Novo Nordisk Foundation Tandem Program (grant number NNF21OC0066950 ), Lundbeck Foundation (for AWO), and The Danish Council for Independent Research ( Danmarks Frie Forskningsfond , two project grants for NO and a Sapera Aude Talent Grant [ DFF-4092-00122 ] for TK). Work in SBK's laboratory was supported by the NIH R01 grant ( HL-125816 ), LEO Foundation Grant ( LF-OC-20-000351 ), NYU Cancer Center Pilot Grant ( P30CA016087 ). All authors read, commented on, and approved the manuscript.

Publisher Copyright:
© 2021 The Authors

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