白介素-12 和白介素-23 通路抑制在炎症性肠病中的作用。
IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.
机构信息
University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium.
KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium.
出版信息
Nat Rev Gastroenterol Hepatol. 2023 Jul;20(7):433-446. doi: 10.1038/s41575-023-00768-1. Epub 2023 Apr 17.
Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn's disease and ulcerative colitis.
白细胞介素-12（IL-12）和白细胞介素-23（IL-23）属于细胞因子白细胞介素-12 家族，在肠道稳态和炎症中起关键作用，并与炎症性肠病的发病机制有关。抗原呈递细胞分泌它们后，会发挥促炎和抗炎受体介导的作用。对这些生物学效应的理解，特别是由 IL-12 和 IL-23 介导的促炎效应的理解，导致了针对 IL-12 和 IL-23 共同亚基（p40；由 ustekinumab 和 briakinumab 靶向）或 IL-23 特异性亚基（p19；由 risankizumab、guselkumab、brazikumab 和 mirikizumab 靶向）的单克隆抗体的开发。这篇综述总结了细胞因子白细胞介素-12 和白细胞介素-23 的生物学特性，讨论了这些细胞因子在肠道稳态和炎症中的作用，并强调了针对 IL-12 和 IL-23 的药物开发，用于治疗克罗恩病和溃疡性结肠炎。
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