Marc Vocanson

Background 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. Methods 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. Results 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. Conclusions 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.