Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Mol Med Rep. 2013 Nov;8(5):1432-8. doi: 10.3892/mmr.2013.1692. Epub 2013 Sep 18.
In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain self‑tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin‑17 (IL‑17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL‑17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL‑17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL‑17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL‑17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.
在免疫系统中，CD4+CD25+Foxp3+调节性 T 细胞（Tregs）维持自身耐受，而 Th17 细胞介导炎症反应。CD39 表达在自然存在的人类 Tregs 的一个亚群表面，对于限制致病性 Th17 细胞非常重要。进一步的研究表明，Tregs 分化为白细胞介素 17（IL-17）+Foxp3+T 细胞。我们之前的研究表明，过敏性哮喘中存在 Th17 和 Tregs 的失衡；然而，其潜在机制仍知之甚少。本研究采用实时定量 PCR（qPCR）检测 CD4+T 细胞中 CD39 和 CD73 mRNA 水平，采用流式细胞术分析外周血中 CD4+T 细胞和 Tregs 中 IL-17+Foxp3+T 细胞、CD4+T 细胞和 Tregs 表面 CD39 和 CD73 的比例。研究结果表明，中重度哮喘患者中 CD4+Foxp3+IL-17+T 细胞的频率增加。哮喘患者 CD4+T 细胞和 Tregs 表面 CD39 表达缺陷。CD4+T 细胞和 Tregs 表面 CD39 和 CD73 的表达与 Th17 细胞的数量呈负相关。这些结果表明，Tregs 向 IL-17+Foxp3+CD4+T 细胞转化的可塑性增加，CD39+Tregs 的频率降低，以及残余 CD39+Tregs 对 IL-17 产生的抑制作用降低，导致哮喘中 Th17 和 Tregs 的失衡。因此，增强 CD39 活性被假设可以预防哮喘的进展。
