TY - JOUR
T1 - Staphylococcus aureus Induces Signal Transducer and Activator of Transcription 5‒Dependent miR-155 Expression in Cutaneous T-Cell Lymphoma
AU - Willerslev-Olsen, Andreas
AU - Gjerdrum, Lise Mette Rahbek
AU - Lindahl, Lise M
AU - Buus, Terkild B
AU - Pallesen, Emil M H
AU - Gluud, Maria
AU - Bzorek, Michael
AU - Nielsen, Boye S
AU - Kamstrup, Maria R
AU - Rittig, Anne Hald
AU - Bonefeld, Charlotte M
AU - Krejsgaard, Thorbjørn
AU - Geisler, Carsten
AU - Koralov, Sergei B
AU - Litman, Thomas
AU - Becker, Jurgen C
AU - Woetmann, Anders
AU - Iversen, Lars
AU - Odum, Niels
N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - Anti-Bacterial Agents/pharmacology
KW - Cell Line, Tumor
KW - Enterotoxins/toxicity
KW - Humans
KW - Lymphoma, T-Cell, Cutaneous/etiology
KW - MicroRNAs/physiology
KW - STAT5 Transcription Factor/physiology
KW - Skin Neoplasms/etiology
KW - Staphylococcus aureus/pathogenicity
UR - http://www.scopus.com/inward/record.url?scp=85105252917&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2021.01.038
DO - 10.1016/j.jid.2021.01.038
M3 - Journal article
C2 - 33862068
SN - 0022-202X
VL - 141
SP - 2449
EP - 2458
JO - The Journal of investigative dermatology
JF - The Journal of investigative dermatology
IS - 10
ER -