Baker Institute for Animal Health and Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, 235 Hungerford Hill Rd., Ithaca, NY 14853, USA.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 380 South University Ave., Philadelphia, PA 19104-4539, USA.
Immunity. 2019 Apr 16;50(4):851-870. doi: 10.1016/j.immuni.2019.03.011.
The discovery of interleukin (IL)-6 and its receptor subunits provided a foundation to understand the biology of a group of related cytokines: IL-12, IL-23, and IL-27. These family members utilize shared receptors and cytokine subunits and influence the outcome of cancer, infection, and inflammatory diseases. Consequently, many facets of their biology are being therapeutically targeted. Here, we review the landmark discoveries in this field, the combinatorial biology inherent to this family, and how patient datasets have underscored the critical role of these pathways in human disease. We present significant knowledge gaps, including how similar signals from these cytokines can mediate distinct outcomes, and discuss how a better understanding of the biology of the IL-12 family provides new therapeutic opportunities.
白细胞介素 (IL)-6 和其受体亚基的发现为理解一组相关细胞因子的生物学特性奠定了基础：IL-12、IL-23 和 IL-27。这些家族成员利用共享的受体和细胞因子亚基，并影响癌症、感染和炎症性疾病的结局。因此，许多生物学方面都被作为治疗靶点。在这里，我们综述了该领域的里程碑式发现、该家族固有的组合生物学，以及患者数据集如何强调这些通路在人类疾病中的关键作用。我们提出了重要的知识空白，包括这些细胞因子的相似信号如何介导不同的结果，并讨论了更好地理解 IL-12 家族的生物学如何提供新的治疗机会。
