Experimental autoimmune neuritis (EAN), an animal model of human GuillainBarr e syndrome, has long been considered as a T helper (Th) 1 cell-mediated autoimmune disorder. However, deficiency of IFN-c, a signature Th1 cytokine, aggravated EAN, with features of elevated production of IL-17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN. To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/ Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL-17A in cauda equina (CE)-infiltrating cells and splenic mononuclear cells (MNCs) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN. The same pattern was also noticed for the expression of IL-22. The diverse expression profiles of FoxP3, IL-17 receptors A and C were seen in CE-infiltrating cells and splenic MNCs in EAN. These findings indicate a major proinflammatory role of Th17 cells and IL-17A in the pathogenesis of EAN. Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN, so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.

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ABSTRACT. Base excision repair (BER) plays an important role in maintaining genome integrity and anti-cancer drug resistance. Single nucleotide polymorphisms (SNPs) in BER genes were detected in 500 lung cancer patients and 500 cancer-free controls. A logistic regression model was applied to analyze the relationship between lung cancer susceptibility and BER SNPs coupled with a wide range of epidemiological factors in a Chinese population. SNPs including rs25487 in the X-ray repair crosscomplementing group 1 gene, rs1052133 in the 8-oxoguanine DNA glycosylase gene, and rs1136410 in the poly (ADP-ribose) polymerase 1 gene were identified. Multivariate analysis showed that the rs25487-AG genotype was associated with a higher incidence of lung cancer compared with the GG genotype. The rs25487 SNP was associated with the pathological distribution of lung cancer. Moreover, rs1052133-GG was associated with early age of lung cancer onset compared with the CC genotype. Our data demonstrated that the SNPs rs25487 and rs1052133 are risk factors for lung cancer in epidemiologically susceptible Chinese people.

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