Topical corticosteroids inhibit allergic skin inflammation but are ineffective in impeding the formation and expansion of resident memory T cells.

Abstract

Tissue-resident memory T (T_RM ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease. We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal T_RM cells in a preclinical model of ACD to 2,4-dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ T_RM by flow cytometry and RNA sequencing. The impact of TA on T_RM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of T_RM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of T_RM . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T_RM , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T_RM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T_RM re-expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications. Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen-specific T_RM , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.