Peron Jean Pierre S, Yang Kayong, Chen Mei-Ling, Brandao Wesley Nogueira, Basso Alexandre S, Commodaro Alessandra G, Weiner Howard L, Rizzo Luiz V
Clinical Immunology Lab, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 1730. Ed. Biomédicas IV, Cidade Universitária, CEP 05508-900, Sao Paulo, SP, Brazil.
J Neuroimmunol. 2010 Oct 8;227(1-2):10-7. doi: 10.1016/j.jneuroim.2010.06.002. Epub 2010 Jul 2.
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory immune response directed against myelin antigens of the central nervous system. In its murine model, EAE, Th17 cells play an important role in disease pathogenesis. These cells can induce blood-brain barrier disruption and CNS immune cells activation, due to the capacity to secrete high levels of IL-17 and IL-22 in an IL-6+TGF-β dependent manner. Thus, using the oral tolerance model, by which 200 μg of MOG 35-55 is given orally to C57BL/6 mice prior to immunization, we showed that the percentage of Th17 cells as well as IL-17 secretion is reduced both in the periphery and also in the CNS of orally tolerated animals. Altogether, our data corroborates with the pathogenic role of IL-17 and IFN-γ in EAE, as its reduction after oral tolerance, leads to an overall reduction of pro-inflammatory cytokines, such as IL-1α, IL-6, IL-9, IL-12p70 and the chemokines MIP-1β, RANTES, Eotaxin and KC in the CNS. It is noteworthy that this was associated to an increase in IL-10 levels. Thus, our data clearly show that disease suppression after oral tolerance induction, correlates with reduction in target organ inflammation, that may be caused by a reduced Th1/Th17 response.
多发性硬化症（MS）是一种自身免疫性疾病，其特征是针对中枢神经系统髓鞘抗原的炎症性免疫反应。在其小鼠模型实验性自身免疫性脑脊髓炎（EAE）中，Th17细胞在疾病发病机制中起重要作用。这些细胞能够以IL-6 +转化生长因子-β（TGF-β）依赖的方式分泌高水平的白细胞介素-17（IL-17）和白细胞介素-22，从而诱导血脑屏障破坏和中枢神经系统免疫细胞活化。因此，我们采用口服耐受模型，在免疫前给C57BL / 6小鼠口服200μg髓鞘少突胶质细胞糖蛋白（MOG）35-55，结果显示口服耐受动物的外周血和中枢神经系统中Th17细胞的百分比以及IL-17分泌均减少。总之，我们的数据证实了IL-17和干扰素-γ（IFN-γ）在EAE中的致病作用，因为口服耐受后它们的减少导致中枢神经系统中促炎细胞因子如IL-1α、IL-6、IL-9、IL-12p70以及趋化因子巨噬细胞炎性蛋白-1β（MIP-1β）、调节激活正常T细胞表达和分泌因子（RANTES）、嗜酸性粒细胞趋化因子和角质形成细胞趋化因子（KC）的总体减少。值得注意的是，这与IL-10水平的增加有关。因此，我们的数据清楚地表明，口服耐受诱导后的疾病抑制与靶器官炎症的减轻相关，这可能是由Th1 / Th17反应降低引起的。
