CIRI-Centre International de Recherche en Infectiologie, INSERM, U1111, Université Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR 5308, Lyon, France.
Etablissement Français du Sang (EFS) Auvergne Rhône-Alpes, Apheresis Unit, Hôpital Lyon Sud, Pierre Bénite, France.
Allergy. 2024 Jan;79(1):52-64. doi: 10.1111/all.15819. Epub 2023 Aug 4.
Tissue-resident memory T (T ) 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 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 by flow cytometry and RNA sequencing.
The impact of TA on T 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 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 . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T 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 , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.
组织驻留记忆 T 细胞（T 细胞）在过敏性接触性皮炎（ACD）中是有害的，它们导致疾病的慢性和严重性。
我们评估了一种标准的局部皮质类固醇（TCS）治疗，曲安奈德（TA），对 2,4-二硝基氟苯（DNFB）诱导的 ACD 模型中表皮 T 细胞形成、维持和再激活的影响。TA 0.01%在 ACD 反应的不同时间点应用，我们通过流式细胞术和 RNA 测序监测皮肤炎症和跟踪 CD8+ CD69+ CD103+ T 细胞。
TA 对 T 形成的影响取决于治疗方案：（i）在预防模式下，即在致敏小鼠接受挑战之前，TA 短暂抑制效应 T 细胞的浸润和 T 细胞在半抗原挑战时的积累。相比之下，（ii）在治疗模式下，即在 ACD 反应的高峰期，TA 阻断皮肤炎症，但未能阻止 T 的形成。最后，（iii）在主动模式下，即在先前的湿疹病变中，TA 对皮肤 T 的存活没有影响，但在过敏原再次暴露时短暂抑制其再激活程序。事实上，特定的 T 细胞在 TA 停药后逐渐恢复增殖功能，并在组织中扩张，导致过度迭代反应。有趣的是，T 细胞的再扩张与反复应用 TA 诱导的皮肤中半抗原部分清除减少相关。
我们的结果表明 TCS 成功治疗 ACD 炎症，但在阻止过敏原特异性 T 细胞的形成和扩张方面大多无效，这肯定限制了慢性皮炎患者持久耐受的诱导。
