British journal of pharmacology · 2026
Tyrosine kinase 2 inhibition by GL-V9 treats psoriasiform dermatitis via macrophage-helper T-cell modulation.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Leyi, Tu Haiyan, Xu Xiaohe, Li Xiangzheng, Liu Shaowen, Long Rongzhuo, Huang He, Guo Qinglong, Chen Xu, Qiang Lei, He Yuan
Аннотация
BACKGROUND AND PURPOSE: Psoriasis (PsO) is a chronic T lymphocyte-mediated inflammatory disease arising on a polygenic background. GL-V9, a structurally optimized flavonoid with reported anti-inflammatory and anti-fibrotic activities, was investigated as a potential therapeutic agent for PsO.
EXPERIMENTAL APPROACH: The therapeutic and relapse-preventive effects of GL-V9 were evaluated in multiple murine models of psoriasiform inflammation. To define its immunomodulatory actions, we established distinct immune-cell polarization models, including macrophage and T helper cell models, and assessed inflammatory mediator production, immune-cell polarization and intercellular communication within psoriatic lesions. Mechanistic studies further examined the interaction between GL-V9 and tyrosine kinase 2 (TYK2), and the functional relevance of TYK2 using siTYK2-mediated knockdown in bone marrow-derived macrophages and THP-1 cells.
KEY RESULTS: GL-V9 effectively alleviated established psoriasiform dermatitis and reduced disease relapse. Mechanistically, preliminary evidence indicated that GL-V9 binds to the pseudokinase domain of TYK2 and suppresses JAK/STAT activation, thereby reducing the production of pro-inflammatory cytokines and chemokines. In M1 macrophages and T helper 1 (Th1) cells, GL-V9 disrupted TYK2-dependent signalling, altered pathogenic polarization states and weakened inflammatory communication with neighbouring immune cells, collectively restoring a more balanced immune microenvironment.
CONCLUSIONS AND IMPLICATIONS: GL-V9 ameliorates PsO by targeting TYK2-STAT signalling and reshaping macrophage-T helper cell-driven inflammation. These findings support GL-V9 as a promising therapeutic candidate for PsO and other TYK2-mediated inflammatory diseases.
EXPERIMENTAL APPROACH: The therapeutic and relapse-preventive effects of GL-V9 were evaluated in multiple murine models of psoriasiform inflammation. To define its immunomodulatory actions, we established distinct immune-cell polarization models, including macrophage and T helper cell models, and assessed inflammatory mediator production, immune-cell polarization and intercellular communication within psoriatic lesions. Mechanistic studies further examined the interaction between GL-V9 and tyrosine kinase 2 (TYK2), and the functional relevance of TYK2 using siTYK2-mediated knockdown in bone marrow-derived macrophages and THP-1 cells.
KEY RESULTS: GL-V9 effectively alleviated established psoriasiform dermatitis and reduced disease relapse. Mechanistically, preliminary evidence indicated that GL-V9 binds to the pseudokinase domain of TYK2 and suppresses JAK/STAT activation, thereby reducing the production of pro-inflammatory cytokines and chemokines. In M1 macrophages and T helper 1 (Th1) cells, GL-V9 disrupted TYK2-dependent signalling, altered pathogenic polarization states and weakened inflammatory communication with neighbouring immune cells, collectively restoring a more balanced immune microenvironment.
CONCLUSIONS AND IMPLICATIONS: GL-V9 ameliorates PsO by targeting TYK2-STAT signalling and reshaping macrophage-T helper cell-driven inflammation. These findings support GL-V9 as a promising therapeutic candidate for PsO and other TYK2-mediated inflammatory diseases.