Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
Immunobiology. 2011 Sep;216(9):979-87. doi: 10.1016/j.imbio.2011.03.013. Epub 2011 Apr 7.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a chronic inflammatory and demyelinating disease of the CNS. Albino Oxford (AO) rats are resistant to the induction of EAE, while the disease can be readily induced in Dark Agouti (DA) rats. Here we investigated a potential contribution of the CNS milieu in the limitation of the encephalitogenic autoimmune response. EAE was induced by immunization of the respective rat strains with spinal cord homogenate emulsified in complete Freund's adjuvant. AO rats did not exhibit clinical signs after immunization while DA rats developed severe neurologic deficits. Infiltration of immune cells into spinal cords (SC) was evident in both strains 12-14 days after the immunization. EAE lesions of AO rats contained substantially lower numbers of CD4+ T cells and CD11b+ cells compared to those in DA rats. This went together with lower levels of interferon (IFN)-γ and interleukin (IL)-17 in the cells isolated from SC. We found a dramatic increase of CXCL12 expression in SC tissue and microvessels of AO rats, whereas DA rats markedly decreased the expression of this chemokine within their CNS. Administration of the CXCL12 antagonist AMD3100 to a substrain of AO rats that developed a weak EAE led to earlier onset and exacerbation of the disease. These results suggest a role of CXCL12 in down-regulating autoimmune processes in AO rats during EAE. Therapeutic modulation of CXCL12 could be a promising strategy for the treatment of CNS autoimmunity.
实验性自身免疫性脑脊髓炎 (EAE) 是多发性硬化症的一种动物模型，是一种中枢神经系统的慢性炎症和脱髓鞘疾病。白化牛津 (AO) 大鼠对 EAE 的诱导具有抗性，而疾病可以在深褐色阿育王 (DA) 大鼠中轻易诱导。在这里，我们研究了中枢神经系统环境对限制自身免疫性脑炎反应的潜在贡献。通过用完全弗氏佐剂乳化的脊髓匀浆免疫各自的大鼠品系来诱导 EAE。免疫后，AO 大鼠没有出现临床症状，而 DA 大鼠则出现严重的神经功能缺损。免疫后 12-14 天，两种大鼠品系的脊髓 (SC) 中均有免疫细胞浸润。与 DA 大鼠相比，AO 大鼠的 EAE 病变中 CD4+T 细胞和 CD11b+细胞的数量明显减少。这与从 SC 分离的细胞中干扰素 (IFN)-γ和白细胞介素 (IL)-17 的水平较低有关。我们发现 AO 大鼠的 SC 组织和微血管中 CXCL12 的表达明显增加，而 DA 大鼠则明显降低了其 CNS 中的这种趋化因子的表达。将 CXCL12 拮抗剂 AMD3100 施用于发展出弱 EAE 的 AO 大鼠亚系，导致疾病更早发作和加重。这些结果表明，CXCL12 在 EAE 期间在 AO 大鼠中下调自身免疫过程中起作用。CXCL12 的治疗性调节可能是治疗中枢神经系统自身免疫的一种有前途的策略。
