University of Colorado School of Medicine Medical Scientist Training Program Aurora, CO, USA.
Department of Psychiatry, University of Vermont Burlington, VT, USA.
Am J Transl Res. 2014 May 15;6(3):312-9. eCollection 2014.
Inflammation in relapsing remitting multiple sclerosis (RRMS) is hypothesized to provide neuroprotective effects via altered cytokine/neurotrophin homeostasis. The distinct neurotrophin production from specific cell populations has not been systematically studied and is likely of high yield in understanding the complex regulation of MS pathogenesis. Here, we describe how the mainstream therapy interferon-β (IFN-β) modulates neurotrophin expression in T cells isolated from RRMS patients and characterize the neuroprotective capabilities of these factors. We utilize SuperArray gene screen technology to investigate the neurotrophin expression profile of T cells. We demonstrate that IFN-β induces an anti-inflammatory cytokine expression pattern in T cells. Additionally, IFN-β upregulates the expression of a novel neurotrophin receptor, the neurotensin high affinity receptor 1 (NTSR1). NTSR1 is expressed in active demyelinating lesions. Furthermore, we demonstrate that the receptor agonist neurotensin is a potent inducer of human neural stem/progenitor cell survival. Our findings highlight the importance of neurotrophin receptors in RRMS and offer insight into disease pathogenesis as well as the mechanisms of action of IFN-β.
在复发缓解型多发性硬化症（RRMS）中，炎症被假设通过改变细胞因子/神经营养因子的平衡来提供神经保护作用。特定细胞群产生的独特神经营养因子尚未得到系统研究，对于理解 MS 发病机制的复杂调控可能具有很高的价值。在这里，我们描述了主流治疗药物干扰素-β（IFN-β）如何调节 RRMS 患者分离的 T 细胞中的神经营养因子表达，并描述了这些因子的神经保护能力。我们利用 SuperArray 基因筛选技术来研究 T 细胞的神经营养因子表达谱。我们证明 IFN-β 在 T 细胞中诱导抗炎细胞因子表达模式。此外，IFN-β 上调了一种新型神经营养因子受体，即神经降压素高亲和力受体 1（NTSR1）的表达。NTSR1 在活跃的脱髓鞘病变中表达。此外，我们证明受体激动剂神经降压素是人类神经干细胞/祖细胞存活的有效诱导剂。我们的发现强调了神经营养因子受体在 RRMS 中的重要性，并为疾病发病机制以及 IFN-β 的作用机制提供了新的见解。
