Abstract：
Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six-IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ-require the IL-1 receptor accessory protein (IL-1RAcP) as their shared co-receptor. Common features of cytokine signaling include redundancy of signaling pathways, sharing of cytokines and receptors, pleiotropy of the cytokines themselves, and multifaceted immune responses. Accordingly, targeting multiple cytokines simultaneously is an emerging therapeutic strategy and can provide advantages over targeting a single cytokine pathway. Here, we show that two monoclonal antibodies, CAN10 and 3G5, which target IL-1RAcP for broad blockade of all associated cytokines, do so through distinct mechanisms and provide therapeutic opportunities for the treatment of inflammatory diseases.
摘要：
白细胞介素-1（IL-1）-家族细胞因子是炎症的有效调节剂，在先天和适应性免疫系统中协调大量的免疫反应。IL-1家族细胞因子信号转导异常,然而,涉及许多不利的健康影响，如慢性炎症，自身免疫性疾病，和癌症。在细胞因子的IL-1家族中，6-IL-1α，IL-1β,IL-33,IL-36α,IL-36β,和IL-36γ-需要IL-1受体辅助蛋白(IL-1RAcP)作为它们共有的共受体。细胞因子信号的共同特征包括信号通路的冗余,共享细胞因子和受体，细胞因子本身的多效性，和多方面的免疫反应。因此，同时靶向多种细胞因子是一种新兴的治疗策略,可以提供优于靶向单一细胞因子途径的优势.这里,我们显示了两种单克隆抗体，CAN10和3G5，靶向IL-1RAcP广泛阻断所有相关细胞因子，通过不同的机制这样做，并为治疗炎症性疾病提供治疗机会。
