Centre for Inflammatory Diseases, Monash University, and Department of Rheumatology, Monash Health, Clayton, Victoria, Australia.
Department of Medicine, Division of Rheumatology and Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Rheumatol. 2024 Apr;20(4):232-240. doi: 10.1038/s41584-024-01093-w. Epub 2024 Mar 11.
Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.
酪氨酸激酶 2（TYK2）是细胞内信号分子 JAK 激酶家族的一员。通过参与 I 型干扰素、IL-12、IL-23 和 IL-10 的下游信号通路，TYK2 引发了与 JAK1、JAK2 和 JAK3 不同的免疫事件。TYK2 多态性与多种风湿性疾病的易感性有关，包括红斑狼疮和皮肌炎。体外和动物研究证实了这些发现，突出了 TYK2 在目前通过 TYK2 信号传导的细胞因子拮抗剂治疗的疾病中的作用。现在已经在人类疾病中研究了各种 TYK2 抑制剂，其中一种抑制剂 deucravacitinib 现已获准用于治疗银屑病。deucravacitinib 的 II 期试验也报告了在治疗银屑病关节炎和系统性红斑狼疮方面的积极结果，初步安全性特征似乎与 JAK1、JAK2 和 JAK3 抑制剂不同。另外两种 TYK2 抑制剂 brepocitinib 和 ropsacitinib 也处于临床试验的早期阶段。总体而言，TYK2 抑制剂有望治疗一系列独特的自身免疫性疾病，并且其安全性特征可能与其他 JAK 抑制剂不同。
