School of Biological Sciences, University of Ulsan, Ulsan 680-749, Korea.
Immune Netw. 2012 Oct;12(5):176-80. doi: 10.4110/in.2012.12.5.176. Epub 2012 Oct 31.
Although the majority of research on CD137 has been directed to T cells, it is becoming clear that this molecule has distinct functions in other lineages of cells, including non-hematopoietic cells. In particular, emerging evidence suggests that the CD137-its ligand (CD137L) network involving immune cells and non-immune cells, directly or indirectly regulates inflammation in both positive and negative manners. Bidirectional signaling through both CD137 and CD137L is critical in the evolution of inflammation: 1) CD137L signaling plays an indispensible role in the activation and recruitment of neutrophils by inducing the production of proinflammatory cytokines and chemokines in hematopoietic and non-hematopoietic cells such as macrophages, endothelial cells and epithelial cells; 2) CD137 signaling in NK cells and T cells is required for their activation and can influence other cells participating in inflammation via either their production of proinflammatory cytokines or engagement of CD137L by their cell surface CD137: 3) CD137 signaling can suppress inflammation by controlling regulatory activities of dendritic cells and regulatory T cells. As recognition grows of the role of dysregulated CD137 or CD137L stimulation in inflammatory diseases, significant efforts will be needed to develop antagonists to CD137 or CD137L.
虽然 CD137 的大多数研究都集中在 T 细胞上，但越来越明显的是，该分子在其他细胞谱系中具有独特的功能，包括非造血细胞。特别是，新出现的证据表明，CD137-CD137L 网络涉及免疫细胞和非免疫细胞，直接或间接地以正负两种方式调节炎症。CD137 和 CD137L 的双向信号对于炎症的发展至关重要：1）CD137L 信号通过诱导造血和非造血细胞（如巨噬细胞、内皮细胞和上皮细胞）中促炎细胞因子和趋化因子的产生，在中性粒细胞的激活和募集中发挥不可或缺的作用；2）NK 细胞和 T 细胞中的 CD137 信号对于其激活是必需的，并且可以通过其产生促炎细胞因子或其细胞表面 CD137 与 CD137L 的结合来影响参与炎症的其他细胞；3）CD137 信号可以通过控制树突状细胞和调节性 T 细胞的调节活性来抑制炎症。随着人们对失调的 CD137 或 CD137L 刺激在炎症性疾病中的作用的认识不断加深，将需要做出巨大努力来开发针对 CD137 或 CD137L 的拮抗剂。
