Department of Dermatology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
Arch Dermatol Res. 2024 Aug 24;316(8):566. doi: 10.1007/s00403-024-03314-4.
Rosacea is a chronic inflammatory skin disease characterized by facial erythema and telangiectasia. Despite ongoing research, the pathogenesis of rosacea remains incompletely understood, and current therapies are not entirely satisfactory. The JAK/STAT signaling pathway plays an essential role in immunoregulation, inflammation, and neurovascular regulation. Inhibition of the JAK/STAT pathway appears to hold promise as a potential therapy for rosacea. This study aimed to investigate the effects of the JAK inhibitor tofacitinib on rosacea and to preliminarily explore its therapeutic mechanism. To this end, a rosacea-like mouse model was induced using LL37 and treated with a 2% tofacitinib emulsion. The results demonstrated that topical application of tofacitinib significantly ameliorated rosacea-like phenotype, reduced the infiltration of CD4 T cells and mast cells, and suppressed dermal angiogenesis. RT-qPCR analysis revealed a reduction in mRNA expression levels of STAT1, STAT4, and STAT5a in skin lesions following topical tofacitinib treatment. Additionally, three patients diagnosed with erythematotelangiectatic rosacea (ETR) were included in the study and treated with oral tofacitinib, leading to a significant improvement in erythema and flushing symptoms. These findings collectively suggest that tofacitinib alleviates LL37-induced rosacea-like skin inflammation in mice and rosacea skin lesions by inhibiting the JAK/STAT signaling pathway.
酒渣鼻是一种慢性炎症性皮肤病，其特征为面部红斑和毛细血管扩张。尽管正在进行研究，但酒渣鼻的发病机制仍不完全清楚，目前的治疗方法并不完全令人满意。JAK/STAT 信号通路在免疫调节、炎症和神经血管调节中起着至关重要的作用。抑制 JAK/STAT 通路似乎有望成为酒渣鼻的一种潜在治疗方法。本研究旨在探讨 JAK 抑制剂托法替尼对酒渣鼻的影响，并初步探讨其治疗机制。为此，使用 LL37 诱导了一种酒渣鼻样小鼠模型，并使用 2%托法替尼乳剂进行治疗。结果表明，局部应用托法替尼可显著改善酒渣鼻样表型，减少 CD4 T 细胞和肥大细胞的浸润，并抑制真皮血管生成。RT-qPCR 分析显示，局部应用托法替尼后皮肤病变中 STAT1、STAT4 和 STAT5a 的 mRNA 表达水平降低。此外，纳入了 3 名诊断为红斑毛细血管扩张性酒渣鼻（ETR）的患者进行研究，他们接受了口服托法替尼治疗，导致红斑和潮红症状显著改善。这些发现共同表明，托法替尼通过抑制 JAK/STAT 信号通路缓解了 LL37 诱导的小鼠酒渣鼻样皮肤炎症和酒渣鼻皮肤病变。
