Tsiogka Aikaterini, Kyriazopoulou Maria, Kontochristopoulos George, Nicolaidou Electra, Stratigos Alexander, Rigopoulos Dimitris, Gregoriou Stamatios
1st Department of Dermatology-Venereology, Faculty of Medicine, Andreas Sygros Hospital, National and Kapodistrian University of Athens, 16121 Athens, Greece.
J Clin Med. 2022 Jul 29;11(15):4431. doi: 10.3390/jcm11154431.
In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the principal signaling cascade for a large number of cytokines and growth factors and is involved in intracellular signal transduction and subsequent regulation of gene transcription. Current knowledge suggests that the robust activation of the T-helper (Th)-2 [interleukin (IL)-4, IL-5, IL-13, IL-31] and Th22 (IL-22) immune responses in both skin and serum plays a pivotal role in the immunopathogenesis of AD especially at the acute stage, followed by a variable degree of Th1 (interferon-γ, tumor necrosis factor alpha) and Th17 (IL-17) activation in chronic disease. Of note, most of the aforementioned inflammatory cytokines utilize the JAK/STAT pathway for downstream signal transduction, explaining the emerging role of JAK inhibitors in the therapeutic armamentarium of AD. The present systematic review aims to discuss the involvement of JAK/STAT pathway in the pathogenesis of AD and summarize the clinical data available on the efficacy and safety of JAK inhibitors which have been used in the treatment of AD thus far.
近年来，对特应性皮炎（AD）发病机制的认识不断拓宽，促使了新型治疗分子的研发，这些分子靶向该疾病的核心炎症成分。 Janus激酶（JAK）/信号转导及转录激活因子（STAT）通路构成了大量细胞因子和生长因子的主要信号级联反应，并参与细胞内信号转导及随后的基因转录调控。目前的知识表明，皮肤和血清中T辅助（Th）-2 [白细胞介素（IL）-4、IL-5、IL-13、IL-31]和Th22（IL-22）免疫反应的强烈激活在AD的免疫发病机制中起关键作用，尤其是在急性期，随后在慢性疾病中会出现不同程度的Th1（干扰素-γ、肿瘤坏死因子α）和Th17（IL-17）激活。值得注意的是，上述大多数炎性细胞因子利用JAK/STAT通路进行下游信号转导，这解释了JAK抑制剂在AD治疗手段中日益凸显的作用。本系统评价旨在探讨JAK/STAT通路在AD发病机制中的作用，并总结目前已用于治疗AD的JAK抑制剂的疗效和安全性方面的临床数据。
