Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
University of Pittsburgh, Division of Rheumatology & Clinical Immunology, Pittsburgh, PA, USA.
Nat Immunol. 2019 Dec;20(12):1594-1602. doi: 10.1038/s41590-019-0514-y. Epub 2019 Nov 19.
IL-17 is a highly versatile pro-inflammatory cytokine crucial for a variety of processes, including host defense, tissue repair, the pathogenesis of inflammatory disease and the progression of cancer. In contrast to its profound impact in vivo, IL-17 exhibits surprisingly moderate activity in cell-culture models, which presents a major knowledge gap about the molecular mechanisms of IL-17 signaling. Emerging studies are revealing a new dimension of complexity in the IL-17 pathway that may help explain its potent and diverse in vivo functions. Discoveries of new mRNA stabilizers and receptor-directed mRNA metabolism have provided insights into the means by which IL-17 cooperates functionally with other stimuli in driving inflammation, whether beneficial or destructive. The integration of IL-17 with growth-receptor signaling in specific cell types offers new understanding of the mitogenic effect of IL-17 on tissue repair and cancer. This Review summarizes new developments in IL-17 signaling and their pathophysiological implications.
IL-17 是一种多功能的促炎细胞因子，对于多种过程至关重要，包括宿主防御、组织修复、炎症性疾病的发病机制和癌症的进展。与体内的深远影响相比，IL-17 在细胞培养模型中表现出惊人的适度活性，这是关于 IL-17 信号转导的分子机制的一个主要知识空白。新兴的研究揭示了 IL-17 途径的一个新的复杂性维度，这可能有助于解释其在体内的强大和多样化功能。新的 mRNA 稳定剂和受体导向的 mRNA 代谢的发现为 IL-17 与其他刺激因素在驱动炎症（无论是有益的还是破坏性的）方面协同作用的方式提供了新的见解。IL-17 与特定细胞类型中的生长受体信号的整合提供了对 IL-17 对组织修复和癌症的有丝分裂作用的新认识。本综述总结了 IL-17 信号转导的新进展及其病理生理学意义。
