Lu Yanming, Guo Yinshi, Xu Linyun, Li Yaqin, Cao Lanfang
Department of Pediatrics, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Shandongzhong Road, Shanghai, 200001, China,
Mol Cell Biochem. 2015 May;403(1-2):25-31. doi: 10.1007/s11010-015-2333-2. Epub 2015 Jan 31.
Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFβ1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma.
气道的慢性炎症性疾病会引发哮喘。调节性T细胞（Treg细胞）和自然杀伤T细胞（NKT细胞）在哮喘的发病机制中均发挥着关键作用。Treg细胞的激活需要Foxp3，然而Foxp3是否可调节Treg细胞与NKT细胞的比例以影响哮喘尚不确定。在卵清蛋白（OVA）诱导的哮喘小鼠模型中，我们通过慢病毒介导的外源性Foxp3强制表达来增加Treg细胞，或者用其激活剂α-半乳糖神经酰胺（α-GalCer）刺激来增加NKT细胞。我们发现，通过强制表达Foxp3使CD4+CD25+ Treg细胞增加，而α-GalCer使其减少；通过强制表达Foxp3使CD3+CD161+ NKT细胞减少，而α-GalCer使其增加。此外，强制表达Foxp3而非α-GalCer可显著减轻哮喘的特征。再者，在OVA处理的肺中，强制表达Foxp3会使IL-10和TGFβ1水平升高，而α-GalCer会使IL-4和INFγ水平升高。综上所述，我们的研究表明，Foxp3可能在哮喘中激活Treg细胞并抑制NKT细胞。Treg细胞和NKT细胞在哮喘中可能相互拮抗彼此的作用。
