Division of Infectious Diseases, Department of Medicine, University of California Irvine, Irvine, CA, USA.
Department of Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA.
Sci Rep. 2017 Feb 17;7:42584. doi: 10.1038/srep42584.
The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation. We have also established that 2-AG levels are upregulated in the serum and in the lymph node of mice during vaccination. We hypothesized that the intrinsic release of eCBs from immune cells during activation by pathogenic antigens mitigate inflammation, but also suppress overall innate and adaptive immune response. Here we demonstrate, for the first time, that transient administration of the cannabinoid receptor 2 antagonist AM630 (10 mg/kg) or inverse agonist JTE907 (3 mg/kg) during immunization heightens the intensity and breadth of antigen-specific immune responses in young and aged mice through the upregulation of immunomodulatory genes in secondary lymphoid tissues.
疫苗的主要特点是能够预防传染性病原体的传播，因此是一种非常宝贵的公共卫生工具。尽管疫苗具有医学相关性，但我们对于调节先天和适应性免疫应答的生理因素的了解仍存在差距。内源性大麻素（eCB）系统是脊椎动物体内平衡的关键调节剂。我们的研究结果表明，抗原激活后巨噬细胞和树突状细胞会产生内源性大麻素 2-花生四烯酸甘油（2-AG）。我们还发现，在接种疫苗期间，小鼠的血清和淋巴结中的 2-AG 水平上调。我们假设，在致病性抗原激活过程中，免疫细胞内源性释放的 eCB 可以减轻炎症，但也会抑制整体先天和适应性免疫应答。在这里，我们首次证明，在免疫接种期间，短暂给予大麻素受体 2 拮抗剂 AM630（10mg/kg）或反向激动剂 JTE907（3mg/kg），通过上调次级淋巴组织中的免疫调节基因，可增强年轻和老年小鼠的抗原特异性免疫应答的强度和广度。
