背景:组织驻留记忆T(TRM)细胞对过敏性接触性皮炎(ACD)有害,它们有助于疾病的慢性和严重程度。
方法:我们评估了标准外用皮质类固醇(TCS)治疗的影响,曲安奈德(TA),在编队上,2,4-二硝基氟苯ACD临床前模型中表皮TRM细胞的维持和再活化。在ACD反应的不同时间点应用TA0.01%,我们监测皮肤炎症并通过流式细胞术和RNA测序跟踪CD8+CD69+CD103+TRM。
结果:TA对TRM形成的影响取决于治疗方案:(i)在预防模式下,也就是说,在攻击前的致敏小鼠中,TA在半抗原攻击时瞬时抑制效应T细胞的浸润和TRM的积累。相比之下,(ii)在治疗模式下,也就是说,在ACD反应的峰值,TA阻断皮肤炎症,但未能阻止TRM的形成。最后,(iii)在主动模式下,也就是说,以前的湿疹病变,TA对皮肤TRM的存活没有影响,但在过敏原再暴露时暂时抑制了它们的再激活程序。的确,特定的TRM在TA停药后逐渐恢复增殖功能并在组织中扩张,导致夸张的迭代反应。有趣的是,TRM再扩增与重复施用TA诱导的半抗原部分从皮肤清除减少相关。
结论:我们的结果表明,TCS成功治疗ACD炎症,但在阻碍过敏原特异性TRM的形成和扩展方面大多无效,这无疑限制了慢性皮炎患者持久耐受的诱导。
Tissue-resident memory T (TRM ) 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 TRM 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+ TRM by flow cytometry and RNA sequencing.
The impact of TA on TRM 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 TRM 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 TRM . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin TRM , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific TRM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, TRM 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 TRM , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.