Barros Priscila O, Dias Aleida S O, Kasahara Taissa M, Ornelas Alice M M, Aguiar Renato S, Leon Soniza A, Ruiz Anne, Marignier Romain, Araújo Ana Carolina R A, Alvarenga Regina, Bento Cleonice A M
Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Brazil.
Departament of Genetics, Federal University of Rio de Janeiro, Brazil.
J Neuroimmunol. 2017 Jun 15;307:82-90. doi: 10.1016/j.jneuroim.2017.04.001. Epub 2017 Apr 7.
Different microbial antigens, by signaling through toll-like receptors (TLR), may contribute to Th17-mediated autoimmune diseases, such as neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to determine the proportion of different Th17-like cell subsets that express TLR in NMOSD patients. For this study, the frequency of different Th17 cell subsets expressing TLR subsets in healthy individuals (n=20) and NMOSD patients (n=20) was evaluated by cytometry. The peripheral levels of soluble CD14 (sCD14) and cytokines were determined by ELISA. Our results demonstrated that the proportion of peripheral CD4 T cells expressing TLR2, 4 and 9 was significantly higher in NMOSD samples than in healthy subjects. In NMOSD, these cells are CD28PD-1CD57 and produce elevated levels of IL-17. Among different TLRs Th17-like subsets, the proportion of those that co-express IL-17 and IL-6 was significantly higher in NMOSD patients, which was positively correlated with sCD14 levels and EDSS score. By contrast, the percentage of TLRsTreg17 cells (IL-10IL-17) was negatively related to sCD14 and the severity of NMOSD. In conclusion, the expansion of peripheral IL-6-producing TLR Th17-like cells in NMOSD patients was associated with both bacterial translocation and disease severity.
不同的微生物抗原通过Toll样受体（TLR）发出信号，可能导致Th17介导的自身免疫性疾病，如视神经脊髓炎谱系障碍（NMOSD）。本研究的目的是确定NMOSD患者中表达TLR的不同Th17样细胞亚群的比例。在本研究中，通过细胞计数法评估了健康个体（n = 20）和NMOSD患者（n = 20）中表达TLR亚群的不同Th17细胞亚群的频率。通过酶联免疫吸附测定法测定可溶性CD14（sCD14）和细胞因子的外周水平。我们的结果表明，NMOSD样本中表达TLR2、4和9的外周CD4 T细胞比例显著高于健康受试者。在NMOSD中，这些细胞为CD28PD-1CD57，并产生升高水平的IL-17。在不同的TLR Th17样亚群中，共表达IL-17和IL-6的亚群比例在NMOSD患者中显著更高，这与sCD14水平和扩展残疾状态量表（EDSS）评分呈正相关。相比之下，TLR Treg17细胞（IL-10IL-17）的百分比与sCD14及NMOSD的严重程度呈负相关。总之，NMOSD患者外周产生IL-6的TLR Th17样细胞的扩增与细菌移位和疾病严重程度均相关。
