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CD8+ tissue-resident memory T cells recruit neutrophils that are essential for flare-ups in contact dermatitis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Background: Allergic contact dermatitis (ACD) is classically described as a delayed-type hypersensitivity reaction. However, patients often experience flare-ups characterized by itching erythema, edema, and often vesicles occurring within hours after re-exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin-resident memory T (TRM) cells play a central role in ACD. However, the pathogenic role of TRM cells in allergen-induced flare-ups is not known. Methods: By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal TRM cells in flare-up reactions to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of TRM cells, neutrophils, and CXCL1/CXCL2 in the response. Results: We show that CD8+ TRM cells initiate massive infiltration of neutrophils in the epidermis within 12 h after re-exposure to the contact allergen. Depletion of neutrophils before re-exposure to the allergen abrogated the flare-up reactions. Furthermore, we demonstrate that CD8+ TRM cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C-X-C chemokine receptor type 1 and 2 inhibits flare-up reactions and neutrophil infiltration. Conclusion: As the first, we show that epidermal CD8+ TRM cells cause ACD flare-ups by rapid recruitment of neutrophils to the epidermis.

OriginalsprogEngelsk
TidsskriftAllergy: European Journal of Allergy and Clinical Immunology
ISSN0105-4538
DOI
StatusAccepteret/In press - 2021

Bibliografisk note

Funding Information:
Conceptualization of this study was led by ABF and CMB supported by JDJ, CG, NØ, and AW. Formal analysis was led by ABF supported by VM. Funding acquisition was done by CMB and JDJ. Investigation was led by ABF supported by VM, AG, MHJ, and JFW. Methodology was led by ABF and CMB supported by CG. Project administration was done by ABF. Resources was obtain by CMB and CG. Supervision was done by CMB supported by JDJ. Validation was led by ABF supported by VM, AG, MHJ, and JFW. Visualization was done by ABF. Writing of the original draft was done by ABF, CMB, and CG. Review and editing was done by all authors.

Funding Information:
This work is supported by the LEO Foundation, the Danish Research Council and the A.P. Møller Foundation for the Advancement of Medical Science and the Danish Environmental Protection Agency as part of the Chemicals Act. The study was performed as part of the collaboration in the Clinical Academic Group Allergy, Copenhagen Health Science Partners.

Publisher Copyright:
© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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