免疫学
单克隆抗体
细胞因子
银屑病
白细胞介素17
炎症
医学
疾病
白细胞介素
发病机制
抗体
病理
作者
Jesper Falkesgaard Højen,Marie Louise Vindvad Kristensen,Amy S. McKee,Megan Taylor Wade,Tania Azam,Lars Lunding,Dennis M. de Graaf,Benjamin J Swartzwelter,Michael Wegmann,Martin Tolstrup,Karsten Beckman,Mayumi Fujita,Stephan Fischer,Charles A. Dinarello
标识
DOI:10.1038/s41590-019-0467-1
摘要
Interleukin (IL)-1R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β and IL-36γ). In many diseases, multiple cytokines contribute to disease pathogenesis. For example, in asthma, both IL-33 and IL-1 are of major importance, as are IL-36 and IL-1 in psoriasis. We developed a blocking monoclonal antibody (mAb) to human IL-1R3 (MAB-hR3) and demonstrate here that this antibody specifically inhibits signaling via IL-1, IL-33 and IL-36 in vitro. Also, in three distinct in vivo models of disease (crystal-induced peritonitis, allergic airway inflammation and psoriasis), we found that targeting IL-1R3 with a single mAb to mouse IL-1R3 (MAB-mR3) significantly attenuated heterogeneous cytokine-driven inflammation and disease severity. We conclude that in diseases driven by multiple cytokines, a single antagonistic agent such as a mAb to IL-1R3 is a therapeutic option with considerable translational benefit.
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