Keratinocytes present Staphylococcus aureus enterotoxins and promote malignant and non-malignant T cell proliferation in cutaneous T cell lymphoma.

Détails

ID Serval
serval:BIB_96839F5A8257
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Keratinocytes present Staphylococcus aureus enterotoxins and promote malignant and non-malignant T cell proliferation in cutaneous T cell lymphoma.
Périodique
The Journal of investigative dermatology
Auteur⸱e⸱s
Zeng Z., Vadivel C.K., Gluud M., Namini MRJ, Yan L., Ahmad S., Hansen M.B., Coquet J., Mustelin T., Koralov S.B., Bonefeld C.M., Woetmann A., Geisler C., Guenova E., Kamstrup M.R., Litman T., Gjerdrum L.R., Buus T.B., Ødum N.
ISSN
1523-1747 (Electronic)
ISSN-L
0022-202X
Statut éditorial
In Press
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Résumé
Cutaneous T-cell lymphoma (CTCL) is characterized by malignant T-cells proliferating in a unique tumor microenvironment (TME) dominated by keratinocytes. Skin colonization and infection by Staphylococcus aureus (S. aureus) is a common cause of morbidity and suspected of fueling disease activity. Here we show that expression of HLA-DR, high-affinity receptors for Staphylococcal enterotoxins (SE), by keratinocytes correlates with IFN-γ expression in the TME. Importantly, IFN-γ induces HLA-DR, SE-binding, and SE-presentation by keratinocytes to malignant T-cells from Sézary syndrome (SS) patients, and malignant and non-malignant T-cell lines derived from SS and Mycosis fungoides patients. Likewise, preincubation of keratinocytes with supernatant from patient-derived SE-producing S. aureus triggers proliferation in malignant T-cells and cytokine release (including IL-2), when cultured with non-malignant T-cells. This is inhibited by pre-treatment with engineered bacteriophage S. aureus-specific endolysins. Furthermore, mutations in the HLA-DR binding sites of SE type-A, and siRNA-mediated knockdown of Janus Kinase-3 (JAK3) and IL-2Rγ block induction of malignant T-cell proliferation. In conclusion, we show that, upon exposure to patient-derived S. aureus and SE, keratinocytes stimulate IL-2Rγ/JAK3-dependent proliferation of malignant and non-malignant T-cells in an environment with non-malignant T-cells. These findings suggest that keratinocytes in the TME play a key role in S. aureus mediated disease activity in CTCL.
Mots-clé
Staphylococcus aureus, cutaneous T cell lymphoma, keratinocyte
Pubmed
Open Access
Oui
Création de la notice
24/05/2024 9:46
Dernière modification de la notice
03/06/2024 7:36
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