特应性皮炎中的组织驻留记忆T细胞：残留炎症、复发及治疗持续性的机制
Tissue-resident memory T cells in atopic dermatitis: mechanisms of residual inflammation, relapse, and therapeutic persistence.
摘要(中文译文)
特应性皮炎（AD）是一种慢性、复发性炎症性皮肤病，其疾病发作常在既往受累的解剖部位反复出现。这一独特的临床模式提示存在残余炎症及持久的局部免疫记忆，且其持续时间超出临床明显缓解期。本文旨在综合现有关于组织驻留记忆T（TRM）细胞在AD发病机制、慢性化及复发中作用的证据，并探讨TRM生物学如何解释治疗撤除后的疾病复发以及为未来治疗策略提供依据。本文对涉及AD及相关慢性皮肤病中TRM分化、持久性、代谢与表观遗传编程、克隆稳定性、微环境交互作用及治疗相关调控的实验性、转化性及临床研究进行叙述性综述。TRM是长寿命、非循环T细胞，通过黏附分子、存活细胞因子、代谢适应及稳定的表观遗传程序滞留于皮肤。在AD中，CD4+和CD8+ TRM均持续存在于皮损及临床消退的皮肤中，并在转录水平保持就绪状态以便快速再激活。临床研究一致表明，停用生物制剂和JAK抑制剂后疾病会复发，支持当前疗法抑制炎症通路但未消除致病性组织记忆这一概念。新出现的数据提示，部分干预措施（包括调节共刺激通路和存活信号）可能部分影响免疫记忆，并在部分患者中延长疾病控制。TRM构成AD残余疾病记忆的核心细胞基础，并为部位特异性复发和治疗抵抗提供了机制解释。可能需要选择性调节致病性TRM及其支持性微环境、同时保留保护性屏障免疫的治疗策略，才能实现持久缓解。
Abstract
Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which disease flares frequently recur at previously affected anatomical sites. This distinctive clinical pattern suggests the presence of residual inflammation and long-lasting local immune memory that persists beyond apparent clinical remission. To synthesize current evidence on the role of tissue-resident memory T (TRM) cells in the pathogenesis, chronicity, and relapse of AD, and to discuss how TRM biology may explain disease recurrence after treatment withdrawal and inform future therapeutic strategies. Narrative review of experimental, translational, and clinical studies addressing TRM differentiation, persistence, metabolic and epigenetic programming, clonal stability, microenvironmental crosstalk, and treatment-related modulation in AD and related chronic dermatoses. TRM are long-lived, non-circulating T cells retained in the skin through adhesion molecules, survival cytokines, metabolic adaptation, and stable epigenetic programs. In AD, both CD4+ and CD8+ TRM persist in lesional and clinically resolved skin and remain transcriptionally poised for rapid reactivation. Clinical studies consistently demonstrate disease relapse after discontinuation of biologics and JAK inhibitors, supporting the concept that current therapies suppress inflammatory pathways without eliminating pathogenic tissue memory. Emerging data suggest that selected interventions, including modulation of costimulatory pathways and survival signals, may partially influence immune memory and prolong disease control in subsets of patients. TRM constitute a central cellular substrate of residual disease memory in AD and provide a mechanistic explanation for site-specific relapse and treatment resistance. Therapeutic strategies that selectively modulate pathogenic TRM and their supporting microenvironment, while preserving protective barrier immunity, may be required to achieve durable remission.
如何引用
AMA
Natalia Zdanowska, Natalia Machoń, Alicja Frączek, Marta Kasprowicz-Furmańczyk, Joanna Czerwińska, Agnieszka Owczarczyk-Saczonek. Tissue-resident memory T cells in atopic dermatitis: mechanisms of residual inflammation, relapse, and therapeutic persistence.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1849265.
APA
Natalia Zdanowska, Natalia Machoń, Alicja Frączek, Marta Kasprowicz-Furmańczyk, Joanna Czerwińska, Agnieszka Owczarczyk-Saczonek (2026). Tissue-resident memory T cells in atopic dermatitis: mechanisms of residual inflammation, relapse, and therapeutic persistence.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1849265
GB/T 7714
Natalia Zdanowska, Natalia Machoń, Alicja Frączek, Marta Kasprowicz-Furmańczyk, Joanna Czerwińska, Agnieszka Owczarczyk-Saczonek. Tissue-resident memory T cells in atopic dermatitis: mechanisms of residual inflammation, relapse, and therapeutic persistence.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1849265.
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