Transcriptomic rewiring of the JAK–STAT pathway in circulating CD4⁺CLA⁺ and CD4⁺ naïve T cells from patients with atopic dermatitis and psoriasis

Abstract

Background – 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 CD4+CLA+ and CD4+ naïve T cells from patients with AD and Ps to find shared and unique molecular signatures associated with the diseases. Methods – Circulating CD4+CLA+ and CD4+ naïve T cells were sorted from the peripheral blood mononuclear cells of patients with AD (n = 11), those with Ps (n = 10), and healthy individuals (n = 11), followed by assay for transposase-accessible chromatin sequencing (ATAC-seq) and mRNA sequencing and data analyses. Results – Transcriptomic and epigenetic landscapes differed markedly between CD4+CLA+ 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. Conclusion – Both CD4+CLA+ 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.