特应性皮炎和银屑病患者循环CD4+CLA+和CD4+幼稚T细胞中JAK-STAT通路的转录组学重排
{"_":"Transcriptomic rewiring of the JAK-STAT pathway in circulating CD4CLA and CD4 naïve T cells from patients with atopic dermatitis and psoriasis.","sup":["+","+","+"]}
摘要(中文译文)
皮肤归巢的皮肤淋巴细胞相关抗原（CLA）表达性T细胞在特应性皮炎（AD）和银屑病（Ps）的发病机制中发挥关键作用。我们旨在表征AD和Ps患者循环CD4CLA和CD4初始T细胞的转录组和表观遗传学图谱，以寻找与这些疾病相关的共享和独特的分子特征。从AD患者（=11）、Ps患者（=10）和健康个体（=11）的外周血单个核细胞中分选循环CD4CLA和CD4初始T细胞，随后进行转座酶可及性染色质测序（ATAC-seq）和mRNA测序及数据分析。CD4CLA和CD4初始T细胞之间的转录组和表观遗传学景观存在显著差异。在AD和Ps中，这些细胞群体内的转录组改变均较为显著，而染色质可及性的变化相对温和。在CLA T细胞中，AD和Ps患者表现出参与T细胞活化、细胞周期和JAK-STAT信号传导的基因表达改变。这些效应在AD中更为明显，而在Ps中则观察到与先天免疫激活更强的关联。值得注意的是，CD4初始T细胞在AD和Ps中也表现出与疾病相关的转录组变化，包括JAK-STAT通路的改变以及IL-2受体组分表达的变化。表观遗传学分析进一步揭示了与免疫调节相关转录因子相连的疾病相关染色质区域。CD4CLA和CD4初始T细胞在AD和Ps中均表现出转录组和表观遗传学改变，提示慢性炎症环境的影响导致了共享和疾病特异性变化，包括两种疾病中JAK-STAT通路的转录组重编程。
Abstract
Skin-homing cutaneous lymphocyte-associated antigen (CLA)-expressing T cells play a key role in the pathogenesis of atopic dermatitis (AD) and psoriasis (Ps). We aimed to characterize the transcriptomic and epigenetic profiles of circulating CD4CLA and CD4 naïve T cells from patients with AD and Ps to find shared and unique molecular signatures associated with the diseases. Circulating CD4CLA and CD4 naïve T cells were sorted from the peripheral blood mononuclear cells of patients with AD ( = 11), those with Ps ( = 10), and healthy individuals ( = 11), followed by assay for transposase-accessible chromatin sequencing (ATAC-seq) and mRNA sequencing and data analyses. Transcriptomic and epigenetic landscapes differed markedly between CD4CLA and CD4 naïve T cells. In both AD and Ps, transcriptomic alterations within these cell populations were substantial, whereas changes in chromatin accessibility were relatively modest. In CLA T cells, patients with AD and Ps exhibited altered expression of genes involved in T-cell activation, cell cycle, and JAK-STAT signaling. These effects were more pronounced in AD, while a stronger association with innate immune activation was seen in Ps. Notably, CD4 naïve T cells also exhibited disease-associated transcriptomic changes in both AD and Ps, including alterations in the JAK-STAT pathway and changes in the expression of IL-2 receptor components. Epigenetic profiling further revealed disease-associated chromatin regions linked to transcription factors involved in immune regulation. Both CD4CLA and CD4 naïve T cells exhibit transcriptomic and epigenetic alterations in AD and Ps, suggesting the influence of the chronic inflammatory milieu leading to shared and disease-specific changes, including transcriptomic rewiring of the JAK-STAT pathway in both diseases.
如何引用
AMA
Martin Pook, Regina Maruste, Peep Kolberg, Kaur Alasoo, Tõnis Org, Liisi Raam, et al. {"_":"Transcriptomic rewiring of the JAK-STAT pathway in circulating CD4CLA and CD4 naïve T cells from patients with atopic dermatitis and psoriasis.","sup":["+","+","+"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1782684.
APA
Martin Pook, Regina Maruste, Peep Kolberg, Kaur Alasoo, Tõnis Org, Liisi Raam, et al (2026). {"_":"Transcriptomic rewiring of the JAK-STAT pathway in circulating CD4CLA and CD4 naïve T cells from patients with atopic dermatitis and psoriasis.","sup":["+","+","+"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1782684
GB/T 7714
Martin Pook, Regina Maruste, Peep Kolberg, Kaur Alasoo, Tõnis Org, Liisi Raam, et al. {"_":"Transcriptomic rewiring of the JAK-STAT pathway in circulating CD4CLA and CD4 naïve T cells from patients with atopic dermatitis and psoriasis.","sup":["+","+","+"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1782684.
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