192 Impact of topical corticosteroids on the formation and expansion of skin resident memory T cells in allergic contact dermatitis

Abstract

Tissue-resident memory T (Trm) cells are detrimental in numerous chronic inflammatory diseases, including allergic contact dermatitis (ACD), in which they re-instigate and augment the immunopathology. We assessed the impact of a standard corticosteroid treatment, topical triamcinolone acetonide, on the formation, maintenance and reactivation of skin Trm cells in ACD. We used an experimental model of ACD, i.e. contact hypersensitivity (CHS), to 2,4-dinitrofluorobenzene that is mediated by allergen-specific CD8+ T cells. Our data show that the impact of triamcinolone acetonide on Trm formation is largely dependent on the treatment regimen. When applied in preventive mode in sensitized animals, the corticosteroid inhibited the infiltration of effector T cells and the accumulation of CD8+ CD69+ CD103+ Trm into the skin. In contrast, the drug failed to prevent Trm differentiation and accumulation, when administrated at the peak of the ACD/CHS inflammation. The application of triamcinolone acetonide also had no effect on the survival of skin Trm persisting in a previous eczema lesion, but it inhibited their reactivation program and the release of key inflammatory mediators such as IFN-g, upon allergen re-exposure. However, this effect was transient, and specific Trm progressively regained proliferative functions and expanded in the tissue, which leaded to exaggerated iterative responses. Our results thus demonstrate that topical corticosteroids successfully cure ACD inflammation, but are chiefly inefficient to hamper the formation and expansion of allergen-specific Trm in the skin, which certainly fails to induce a long-lasting tolerance in patients.