Krejsgaard, Thorbjørn Frej9; Willerslev-Olsen, Andreas9; Lindahl, Lise Maria3; Bonefeld, Charlotte Menne9; Koralov, Sergei B.4; Geisler, Carsten10; Wasik, Mariusz A.5; Gniadecki, Robert6; Kilian, Mogens7; Iversen, Lars8; Andersen, Anders Woetmann9; Ødum, Niels9
1 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet3 Dermato-Venerologisk Afdeling S4 New York University School of Medicine5 University of Pennsylvania6 Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark;7 Department of Biomedicine, Aarhus University, Aarhus, Denmark.8 Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark;9 Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet10 Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet
Patients with cutaneous T-cell lymphoma (CTCL) are frequently colonized with Staphylococcus aureus (SA). Eradication of SA is, importantly, associated with significant clinical improvement suggesting that SA promotes the disease activity but the underlying mechanisms remain poorly characterized. Here we show that SA isolates from involved skin express staphylococcal enterotoxins (SEs) which induce cross-talk between malignant and benign T cells leading to Stat3-mediated IL-10 production by the malignant T cells. The SEs did not stimulate the malignant T cells directly. Instead, SEs triggered a cascade of events involving cell-cell and asymmetric cytokine interactions between malignant and benign T cells, which stimulated the malignant T cells to express high levels of IL-10. Much evidence supports that malignant activation of the Stat3/IL-10 axis plays a key role in driving the immune dysregulation and severe immunodeficiency that characteristically develops in CTCL patients. The present findings thereby establish a novel link between SEs and immune dysregulation in CTCL strengthening the rationale for antibiotic treatment of colonized patients with severe or progressive disease.