| Title: |
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; Sørensen, Erik; Rantakari, Pia; Bonefeld, Charlotte Menne; Geisler, Carsten; Woetmann, Anders; Lahesmaa, Riitta; Iversen, Lars; Wolf, Peter; Litman, Thomas; Buus, Terkild B.; Ødum, Niels |
| Source: |
Gluud, M, Pallesen, E M, Zeng, Z, Namini, M R J, Vadivel, C K, Gjerdrum, L M R, Yan, L, Ahmad, S, Lindahl, L M, Bzorek, M, Kamstrup, M R, Dey, S, Ostrowski, S R, Sørensen, E, Rantakari, P, Bonefeld, C M, Geisler, C, Woetmann, A, Lahesmaa, R, Iversen, L, Wolf, P, Litman, T, Buus, T B & Ødum, N 2026, 'Staphylococcus aureus Augments Epithelial Skin Barrier Damage Through T Cell Activation in Cutaneous T Cell Lymphoma', Allergy: European Journal of Allergy and Clinical Immunology. https://doi.org/10.1111/all.70292 |
| Publication Year: |
2026 |
| Collection: |
Aarhus University: Research |
| Subject Terms: |
barrier; epithelium; infections; inflammation; T cells |
| Description: |
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. Methods: We 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. Results: S. 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. Conclusions: 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0105-4538; 1398-9995 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41795941; info:eu-repo/semantics/altIdentifier/pissn/0105-4538; info:eu-repo/semantics/altIdentifier/eissn/1398-9995 |
| DOI: |
10.1111/all.70292 |
| Availability: |
https://pure.au.dk/portal/en/publications/d1c4cace-c974-4c8a-8c45-28074a34d8b2; https://doi.org/10.1111/all.70292; https://www.scopus.com/pages/publications/105032153820 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.4BC292B4 |
| Database: |
BASE |