Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
Cannabis Cannabinoid Res. 2021 Aug;6(4):300-314. doi: 10.1089/can.2020.0046. Epub 2020 Oct 30.
Activation of the peripheral immune system and the infiltration of immune cells into the central nervous system are both key features of the experimental autoimmune encephalomyelitis (EAE) model. By exploring how the endocannabinoid system works to modulate this response, we can better understand how exogenous cannabinoids, such as THC, might be used to modulate the immune responses of multiple sclerosis patients. In this study, we examined the role of the CB receptor in IFN-γ and IL-17A production in the EAE model and stimulations of naive splenocytes using mice and wild-type (WT) littermates. We also introduce a novel method of scoring spinal cord histological sections to show the differences in disease severity between and WT mice with EAE. Clinical scores of EAE and WT/EAE mice showed more severe disease progression in mice, which was confirmed using our new histological scoring method. In the peripheral immune system, IFN-γ production by restimulated splenocytes from /EAE mice, compared with WT/EAE mice, was increased and the primary source of IFN-γ was a CD3 cell population; however, IFN-γ production by splenocytes was decreased compared with WT splenocytes when the primary source of IFN-γ was CD3 T cells in cultures from naive mice stimulated by either anti-CD3/anti-CD28 antibodies or Staphylococcal superantigens. These findings suggest a duality to the CB receptor's effects on the peripheral immune response, which varies based on the specific cell types stimulated. Knowledge of the complex nature of a receptor is an important part of determining its potential usefulness as a therapeutic target, and these findings further define the role of CB in IFN-γ responses.
外周免疫系统的激活和免疫细胞浸润中枢神经系统是实验性自身免疫性脑脊髓炎（EAE）模型的两个关键特征。通过探索内源性大麻素系统如何调节这种反应，我们可以更好地了解外源性大麻素，如 THC，如何用于调节多发性硬化症患者的免疫反应。在这项研究中，我们研究了 CB 受体在 IFN-γ 和 IL-17A 产生中的作用在 EAE 模型和使用 和野生型（WT）同窝仔鼠的幼稚脾细胞刺激中。我们还介绍了一种新的脊髓组织学切片评分方法，以显示 EAE 和 WT/EAE 小鼠之间疾病严重程度的差异。EAE 和 WT/EAE 小鼠的临床评分显示 鼠疾病进展更为严重，这一点通过我们新的组织学评分方法得到了证实。在外周免疫系统中，与 WT/EAE 小鼠相比，/EAE 小鼠再刺激脾细胞产生的 IFN-γ增加，其主要来源是 CD3 细胞群；然而，当用抗 CD3/抗 CD28 抗体或葡萄球菌超抗原刺激来自幼稚小鼠的培养物中的 CD3 T 细胞作为 IFN-γ的主要来源时， 脾细胞产生的 IFN-γ减少。这些发现表明 CB 受体对外周免疫反应的影响具有双重性，这取决于所刺激的特定细胞类型而有所不同。了解受体的复杂性质是确定其作为治疗靶点潜在用途的重要部分，这些发现进一步定义了 CB 在 IFN-γ 反应中的作用。
