The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
Adaptive Biotechnologies Corporation, Seattle, WA, USA.
Allergy. 2017 Dec;72(12):2017-2025. doi: 10.1111/all.13223. Epub 2017 Jun 28.
Atopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and nonlesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to nonlesional skin remains unclear.
We performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 nonlesional AD biopsies, compared to six healthy control and six cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts.
While greater T-cell infiltrates were observed in lesional vs nonlesional AD, TCR repertoire diversity was similar in lesional and nonlesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with nonlesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and nonlesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g., IL-13, CCL17, IL23p19, CXCL10).
While AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and nonlesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T cells well beyond clinically inflamed lesions.
特应性皮炎（AD）的特征是强烈的免疫激活。各种 T 细胞亚群，包括 Th2/Th22 细胞，在病变和非病变皮肤中增加。然而，关于病变 AD 中 T 细胞受体（TCR）库的多样性及其与非病变皮肤的关系，文献存在矛盾。
我们对 29 例病变 AD 和 19 例非病变 AD 活检进行了β-TCR 库的高通量深度测序，与之前发表的 6 例健康对照和 6 例皮肤 T 细胞淋巴瘤（CTCL）样本进行了比较。
虽然病变 AD 中观察到更大的 T 细胞浸润，但病变和非病变组织中的 TCR 库多样性相似，并且独特 T 细胞克隆的绝对数量与相应的 T 细胞计数相关。大多数（87%）病变中扩增最多的 T 细胞克隆与非病变组织共享，并且在成功接受局部曲安奈德治疗 16 周后仍然存在。然而，病变和非病变 AD 均显示出高度多克隆的 TCR 模式，没有证据表明寡克隆扩增，或 AD 皮肤中某些 V-β 基因的优先使用。整体 T 细胞浸润的大小，而不是克隆性的水平，与关键炎症介质（如 IL-13、CCL17、IL23p19、CXCL10）的 mRNA 水平相关。
虽然 AD 具有高度多克隆的 TCR 库，尽管缺乏关于 TCR 抗原特异性的信息，但病变和非病变皮肤之间最丰富的克隆共享，以及它们在数月治疗后仍然存在，表明潜在的致病皮肤驻留记忆 T 细胞持续存在，远远超出临床炎症病变。
