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

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.