Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, 5 E. 98th Street, New York, NY, 10029, USA.
Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.
Am J Clin Dermatol. 2019 Apr;20(2):181-192. doi: 10.1007/s40257-018-0413-2.
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations. While AD is primarily Th2-driven, the clinical and molecular heterogeneity of AD endotypes highlights the unmet need for effective therapeutic options that target more than one immune axis and are safe for long-term use. The JAK inhibitors, which target different combinations of kinases, have overlapping but distinct mechanisms of action and safety profiles. Several topical and oral JAK inhibitors have been shown to decrease AD severity and symptoms. A review of the JAK and SYK inhibitors that are currently undergoing evaluation for efficacy and safety in the treatment of AD summarizes available data on a promising area of therapeutics and further elucidates the complex molecular interactions that drive AD.
特应性皮炎（AD）是最常见的炎症性皮肤病之一。AD 由屏障功能障碍和 T 辅助（Th）2、Th22 的异常免疫激活驱动，以及各种亚型中不同程度的 Th1 和 Th17。Janus 激酶（JAK）-信号转导和转录激活因子（STAT）和脾酪氨酸激酶（SYK）途径参与几种与 AD 相关的细胞因子的信号转导，如 IFN-γ、IL-4、IL-13、IL-31、IL-33、IL-23、IL-22 和 IL-17，介导下游炎症和屏障改变。虽然 AD 主要由 Th2 驱动，但 AD 内型的临床和分子异质性突出表明，需要有效的治疗方法，这些方法不仅要针对多个免疫轴，而且要安全，适合长期使用。JAK 抑制剂针对不同的激酶组合，具有重叠但不同的作用机制和安全性特征。几种局部和口服 JAK 抑制剂已被证明可降低 AD 的严重程度和症状。对目前正在评估治疗 AD 的疗效和安全性的 JAK 和 SYK 抑制剂的综述总结了治疗领域有希望的现有数据，并进一步阐明了驱动 AD 的复杂分子相互作用。
