Department of Physiology, National University of Singapore, Singapore, Singapore.
Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Front Immunol. 2020 Nov 6;11:571964. doi: 10.3389/fimmu.2020.571964. eCollection 2020.
The potent costimulatory effect of CD137 has been implicated in several murine autoimmune disease models. CD137 costimulates and polarizes antigen-specific T cells toward a potent Th1/Tc1 response, and is essential for the development of experimental autoimmune encephalomyelitis (EAE), a murine model of Multiple Sclerosis (MS). This study aimed to investigate a role of CD137 in MS. Immunohistochemical and immunofluorescence staining of MS brain tissues was used to identify expression of CD137. CD137 cells were identified in MS brain samples, with active lesions having the highest frequency of CD137 cells. CD137 expression was found on several leukocyte subsets, including T cells, B cells and endothelial cells. In particular, CD137 B cells were found in meningeal infiltrates. experiments showed that CD137 engagement on activated B cells increased early TNF and persistent IL-6 secretion with increased cell proliferation. These CD137 B cells could interact with CD137L-expressing cells, secrete pro-inflammatory cytokines and accumulate in the meningeal infiltrate. This study demonstrates CD137 expression by activated B cells, enhancement of the inflammatory activity of B cells upon CD137 engagement, and provides evidence for a pathogenic role of CD137 B cells in MS.
CD137 的强烈共刺激作用已被涉及到几种小鼠自身免疫性疾病模型中。CD137 共刺激并将抗原特异性 T 细胞极化到有效的 Th1/Tc1 反应，并且对于实验性自身免疫性脑脊髓炎 (EAE) 的发展至关重要，EAE 是多发性硬化症 (MS) 的小鼠模型。本研究旨在探讨 CD137 在 MS 中的作用。通过免疫组织化学和免疫荧光染色来鉴定 MS 脑组织中的 CD137 表达。在 MS 脑样本中鉴定出 CD137 细胞，活性病变中 CD137 细胞的频率最高。CD137 表达存在于几种白细胞亚群上，包括 T 细胞、B 细胞和内皮细胞。特别是，在脑膜浸润物中发现了 CD137 B 细胞。实验表明，激活的 B 细胞上的 CD137 结合增加了早期 TNF 和持续的 IL-6 分泌，并增加了细胞增殖。这些 CD137 B 细胞可以与表达 CD137L 的细胞相互作用，分泌促炎细胞因子并在脑膜浸润物中积聚。本研究证明了激活的 B 细胞上的 CD137 表达，CD137 结合增强了 B 细胞的炎症活性，并为 CD137 B 细胞在 MS 中的致病作用提供了证据。
