PDF(Pubmed)
Abstract：
The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production-particularly IL-4/13-are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13Rα1 and IL-13Rα2 receptor system. Our study focused on investigating ex vivo skin biopsies in AD (n = 17), CNPG (n = 14) and healthy controls (HC; n = 10), examining the gene expression landscape of interleukins linked with pruritus (IL-13, IL-4, IL-31) and their corresponding receptors. Compared to HC, results revealed a significant upregulation of IL-4, IL-13, and IL-13RA1 in AD, whereas CNPG did not show increased IL13 expression. Notably, the decoy receptor IL-13RA2 displayed intriguing patterns, with AD showing a marked increase compared to both HC and CNPG. Positive correlations between receptor expression and itch intensity and hyperkinesis sensation underscore clinical relevance, potentially serving as biomarkers. The findings suggest a pivotal role of IL-4 and IL-13, along with IL-13RA1, in pruritus pathogenesis in both entities, while IL-13 upregulation in AD is countered by IL-13RA2. The comparable expression of IL-13RA2 to HC in CNPG suggests the absence of this regulatory mechanism, potentially worsening the disease and leading to prolonged scratching behavior. These insights illuminate the intricate interplay of interleukins and receptors in different pruritus phenotypes, laying the groundwork for understanding underlying mechanisms and offering avenues for therapeutic intervention.
摘要：
特应性皮炎(AD)和慢性结节性痒疹(CNPG)的临床表现包括瘙痒和湿疹/皮损,给患者带来重大挑战。以细胞因子产生(特别是IL-4/13)为标志的Th2细胞和ILC2是关键的治疗靶标。尽管显示出剂量依赖性的缺乏瘙痒诱导注射后，IL-13通过IL-13Rα1和IL-13Rα2受体系统起作用。我们的研究重点是调查AD的离体皮肤活检(n=17)，CNPG（n=14）和健康对照（HC；n=10），检查与瘙痒相关的白细胞介素（IL-13，IL-4，IL-31）及其相应受体的基因表达情况。与HC相比，结果显示，在AD中IL-4、IL-13和IL-13RA1显著上调，而CNPG未显示IL13表达增加。值得注意的是,诱饵受体IL-13RA2显示出有趣的模式，与HC和CNPG相比,AD显示显著增加。受体表达与瘙痒强度和运动过度感觉之间的正相关强调了临床相关性，可能作为生物标志物。研究结果表明，IL-4和IL-13以及IL-13RA1在两个实体的瘙痒发病机理中起着关键作用。而IL-13在AD中的上调被IL-13RA2所抵消。IL-13RA2与HC在CNPG中的类似表达表明缺乏这种调节机制，可能使疾病恶化并导致长时间的抓挠行为。这些见解阐明了白细胞介素和受体在不同瘙痒表型中的复杂相互作用，为理解潜在机制和提供治疗干预途径奠定基础。
