Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
J Mol Med (Berl). 2018 Oct;96(10):983-992. doi: 10.1007/s00109-018-1684-z. Epub 2018 Aug 15.
The pleiotropic cytokine IL-1 mediates its biological functions via association with the signaling receptor IL-1R1. Despite an apparent simplicity in IL-1 signaling activation, multiple negative regulators have been identified. The decoy receptor IL-1R2 (also known as CD121b) can suppress IL-1 maturation, sequester its active forms or hinder the signaling complex assembly. IL-1R2 is differentially expressed among numerous cell types and displays cis- and trans- modes of action. In this review, we link different forms of IL-1R2 (membrane-bound (mIL-1R2), secreted (sIL-1R2), shedded (shIL-1R2), cytoplasmic, and intracellular domain (IL-1R2) restricted) with their ability to interfere with IL-1, thereby regulating immune responses. We also discuss the intriguing possible function of IL-1R2 as a transcriptional regulator. Finally, we summarize the known impact of IL-1R2 in disease pathogenesis and discuss its potential role in treatment of inflammatory conditions.
多效细胞因子白细胞介素-1 (IL-1) 通过与信号受体白细胞介素-1 受体 1 (IL-1R1) 结合来发挥其生物学功能。尽管 IL-1 信号激活的机制看似简单，但已经鉴定出多种负调控因子。诱饵受体白细胞介素-1 受体 2 (也称为 CD121b) 可以抑制白细胞介素-1 的成熟，隔离其活性形式或阻碍信号复合物的组装。白细胞介素-1 受体 2 在许多细胞类型中差异表达，并显示顺式和反式作用模式。在这篇综述中，我们将不同形式的白细胞介素-1 受体 2（膜结合型 (mIL-1R2)、分泌型 (sIL-1R2)、脱落型 (shIL-1R2)、胞质型和细胞内结构域型 (IL-1R2))与其干扰白细胞介素-1 的能力联系起来，从而调节免疫反应。我们还讨论了白细胞介素-1 受体 2 作为转录调节剂的有趣的潜在功能。最后，我们总结了白细胞介素-1 受体 2 在疾病发病机制中的已知影响，并讨论了其在炎症性疾病治疗中的潜在作用。
