Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation
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Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation. / Krejsgaard, Thorbjørn Frej; Willerslev-Olsen, Andreas; Lindahl, Lise Maria; Bonefeld, Charlotte Menne; Koralov, Sergei B.; Geisler, Carsten; Wasik, Mariusz A.; Gniadecki, Robert; Kilian, Mogens; Iversen, Lars; Andersen, Anders Woetmann; Ødum, Niels.
In: Blood, Vol. 124, No. 5, 2014, p. 761-70.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation
AU - Krejsgaard, Thorbjørn Frej
AU - Willerslev-Olsen, Andreas
AU - Lindahl, Lise Maria
AU - Bonefeld, Charlotte Menne
AU - Koralov, Sergei B.
AU - Geisler, Carsten
AU - Wasik, Mariusz A.
AU - Gniadecki, Robert
AU - Kilian, Mogens
AU - Iversen, Lars
AU - Andersen, Anders Woetmann
AU - Ødum, Niels
N1 - Copyright © 2014 American Society of Hematology.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2014-01-551184
DO - 10.1182/blood-2014-01-551184
M3 - Journal article
C2 - 24957145
VL - 124
SP - 761
EP - 770
JO - Blood
JF - Blood
SN - 0006-4971
IS - 5
ER -
ID: 117551050