A1 Refereed original research article in a scientific journal
Staphylococcus aureus Augments Epithelial Skin Barrier Damage Through T Cell Activation in Cutaneous T Cell Lymphoma
Authors: Gluud, Maria; Pallesen, Emil M.; Zeng, Ziao; Namini, Martin R. J.; Vadivel, Chella Krishna; Gjerdrum, Lise Mette Rahbek; Yan, Lang; Ahmad, Sana; Lindahl, Lise M.; Bzorek, Michael; Kamstrup, Maria R.; Dey, Saptaswa; Ostrowski, Sisse Rye; Sorensen, Erik; Rantakari, Pia; Bonefeld, Charlotte Menne; Geisler, Carsten; Woetmann, Anders; Lahesmaa, Riitta; Iversen, Lars; Wolf, Peter; Litman, Thomas; Buus, Terkild B.; Odum, Niels
Publication year: 2026
Journal: Allergy
ISSN: 0105-4538
eISSN: 1398-9995
DOI: https://doi.org/10.1111/all.70292
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://onlinelibrary.wiley.com/doi/10.1111/all.70292
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/516087552
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
Background
Skin barrier dysfunction is central to inflammation and susceptibility to infection in atopic dermatitis (AD). Cutaneous T-cell lymphoma (CTCL) shares clinical similarities with AD and is also associated with a high prevalence of Staphylococcus aureus (S. aureus) colonisation. However, the mechanisms driving skin barrier damage in CTCL and the contribution of bacteria remain poorly understood.
MethodsWe investigate how the interplay between S. aureus (and staphylococcal enterotoxins (SEs)) and primary malignant- and non-malignant T cells affects keratinocyte expression of skin barrier proteins; in vitro, in an EL4 murine lymphoma model of bacteria-driven tumour progression, and in CTCL patient lesions colonised with SE-producing S. aureus before and after bacterial eradication by antibiotic treatment.
ResultsS. aureus and SEs activate malignant and non-malignant T cells to release barrier-repressing cytokines, including IL-4, IL-13, IL-22, and OSM, and JAK-dependent downregulation of filaggrin and loricrin in keratinocytes. In the EL4 model, bacteria-colonised tumour-bearing mice show significant filaggrin loss in tumour-adjacent epidermis, whereas antibiotic-treated mice maintain near-normal expression. Clinically, antibiotic eradication of SE-producing S. aureus partially restores filaggrin and loricrin expression in three of four patients, paralleling reduced inflammatory signalling.
SE-producing S. aureus promotes skin barrier impairment in CTCL through cytokine-driven, JAK-dependent repression of structural proteins in keratinocytes. These findings identify microbial–immune crosstalk as a contributor to CTCL skin pathology and provide mechanistic rationale for strategies targeting S. aureus colonisation as adjunctive therapy in CTCL.
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Funding information in the publication:
This research was funded by LEO Foundation through the LEO Foundation Skin Immunology Research Center, Dr. Abildgaard Fellowship (LF-FE-23-700015; T.B.B.), the Danish Cancer Society (Kræftens Bekæmpelse; C.K.V. and N.Ø.) the Fight Cancer Program (Knæk Cancer; R132-A8475; NØ) and donation from Fabrikant Vilhelm Pedersen og Hustrus Legat (Kræftens Bekæmpelse R374-A22434); Novo Nordisk Research Foundation (N.Ø.), Novo Nordisk Foundation Tandem Program—NNF210C0066950 in the call “Tandem Programme 2021” (N.Ø.), the Danish Council for Independent Research (Danmarks Frie Forskningsfond, grant number: 0134-00385B and grant https://doi.org/10.46540/3165-00211B; N.Ø.). RL was funded by Reserach Council of Finland grant 331793 and The Sigrid Jusélius Foundation. Role of the funding source: The funding source had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
