Itch in atopic dermatitis (AD) is aggravated under warm conditions. Transient receptor potential vanilloid (TRPV) 3, a member of the thermosensitive transient receptor potential channels, is activated by innocuous heat and is abundantly expressed in keratinocytes. The potential role of TRPV3 in itch is illustrated in TRPV3 channelopathies of humans and mice. However, the role of TRPV3 in heat-induced itch in AD and the underlying mechanisms are unclear. Here we showed that keratinocytes isolated from patients with AD exhibit enhanced expression and heat sensitivity with hyperactive channel function of TRPV3. Heat stimulus induced enhanced secretion of thymic stromal lymphopoietin, nerve growth factor, and prostaglandin E₂ by keratinocytes from patients with AD through TRPV3 activation. TRPV3 agonists increased thymic stromal lymphopoietin, nerve growth factor, prostaglandin E₂, and IL-33 production in human keratinocytes and induced scratching behavior upon intradermal injection in mice. TRPV3 was upregulated in the skin of MC903-induced AD mouse model. Heat stimulation to MC903-treated mice increased scratching behavior and produced higher levels of thymic stromal lymphopoietin, nerve growth factor, prostaglandin E₂, and IL-33 from the epidermis, which were attenuated by pharmacologic inhibition of TRPV3. Moreover, neutralization of thymic stromal lymphopoietin reduced heat-evoked scratching in MC903-challenged mice. These results suggest that TRPV3 is a potential therapeutic target for heat-induced itch in AD.

在温暖的条件下会加剧特应性皮炎（AD）的瘙痒。热敏瞬态受体电位通道的成员瞬态受体电位香草酸（TRPV）3被无害的热量激活，并在角质形成细胞中大量表达。人类和小鼠的TRPV3通道病变说明了TRPV3在瘙痒中的潜在作用。然而，尚不清楚TRPV3在AD中由热引起的瘙痒中的作用及其潜在机制。在这里，我们显示从AD患者中分离出的角质形成细胞表现出增强的表达和热敏性，并具有TRPV3的过度活跃通道功能。热刺激诱导胸腺基质淋巴细胞生成素，神经生长因子和前列腺素E ₂分泌增加AD患者的角质形成细胞通过TRPV3激活而被激活。TRPV3激动剂可增加人角质形成细胞中的胸腺基质淋巴细胞生成素，神经生长因子，前列腺素E ₂和IL-33的产生，并在小鼠皮内注射后引起抓挠行为。TRPV3在MC903诱导的AD小鼠模型的皮肤中上调。对MC903治疗的小鼠进行热刺激会增加抓挠行为，并产生更高水平的胸腺基质淋巴细胞生成素，神经生长因子，前列腺素E ₂表皮中的IL-33和IL-33，它们被TRPV3的药理抑制作用减弱。此外，胸腺基质淋巴细胞生成素的中和减少了MC903攻击小鼠的热诱发性scratch抓。这些结果表明TRPV3是AD中热诱发瘙痒的潜在治疗靶标。