Litwak Sara A, Payne Natalie L, Campanale Naomi, Ozturk Ezgi, Lee Jae Young, Petratos Steven, Siatskas Christopher, Bakhuraysah Maha, Bernard Claude C A
Multiple Sclerosis Research Group, Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
PLoS One. 2013 Dec 5;8(12):e82101. doi: 10.1371/journal.pone.0082101. eCollection 2013.
The potential role of Nogo-66 Receptor 1 (NgR1) on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/-) animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS)-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM) controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or by MOG35-55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG35-55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG35-55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.
在诸如多发性硬化症（MS）及其动物模型实验性自身免疫性脑脊髓炎（EAE）等神经炎症性疾病中，Nogo-66受体1（NgR1）对免疫细胞表型及其激活的潜在作用尚不清楚。为了进一步了解该受体在造血来源细胞上的功能，我们使用NgR1缺陷型（ngr1-/-）动物进行了表型和功能分析。对血液、脾脏、胸腺、淋巴结、骨髓和中枢神经系统（CNS）浸润血细胞进行的基于流式细胞术的表型分析显示，与野生型同窝对照（WTLM）相比，未致敏的ngr1-/-动物没有免疫缺陷。EAE可通过重组髓鞘少突胶质细胞糖蛋白（rMOG，一种认为B细胞具有致病性的模型）或MOG35-55肽（一种不依赖B细胞的模型）诱导。我们已经证明，在注射MOG35-55的ngr1-/-小鼠中，与WTLM对照相比，EAE严重程度显著降低，这与脊髓中轴突损伤减少相关。然而，尽管在疾病慢性期的ngr1-/-小鼠中枢神经系统中观察到轴突损伤减少，但当使用rMOG作为致脑炎原时，没有临床差异可归因于特定基因型。在MOG35-55诱导EAE后，我们未发现ngr1-/-和WTLM小鼠之间分析的免疫细胞群体有任何重大变化。总体而言，这些数据表明，NgR1对免疫细胞库、其激活以及向中枢神经系统的迁移几乎没有影响。
