Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
J Immunol. 2011 Jan 1;186(1):92-102. doi: 10.4049/jimmunol.1000960. Epub 2010 Dec 3.
Proper transcriptional control of pro- and anti-inflammatory responses of the immune system is important for a fine-tuned balance between protection and tolerance. Emerging evidence suggests a key role for epigenetic regulation in governing the Th cell differentiation, where effector cytokines direct the overall immune response. In this study, we describe a method to pinpoint the location of isolated human CD4(+) T cells on any T cell effector axis based on specific CpG methylation of cytokine and transcription factor loci. We apply the method on CD4(+) cells obtained from rheumatoid arthritis and multiple sclerosis patients and show that synovial fluid infiltrating CD4(+) T cells are committed toward both Th1 and regulatory T cell phenotype, whereas the Th2 response is suppressed. Furthermore, we show that the IL-17A gene is regulated by promoter methylation and that Th17 commitment is not a common feature in the inflamed joints of rheumatoid arthritis patients. We conclude that the method described in this paper allows for accurate profiling of Th lineage commitment in ex vivo-isolated CD4(+) T cells.
适当的转录控制有助于免疫系统的促炎和抗炎反应达到精细的平衡，从而实现保护和耐受。有新证据表明，表观遗传调控在调控 Th 细胞分化中起着关键作用，效应细胞因子决定了整体免疫反应。在这项研究中，我们描述了一种方法，可以根据细胞因子和转录因子基因座的特定 CpG 甲基化，确定分离的人 CD4(+) T 细胞在任何 T 细胞效应轴上的位置。我们将该方法应用于从类风湿关节炎和多发性硬化症患者中获得的 CD4(+)细胞，结果表明，滑膜浸润的 CD4(+) T 细胞既向 Th1 细胞又向调节性 T 细胞表型分化，而 Th2 反应受到抑制。此外，我们还表明，IL-17A 基因受启动子甲基化调控，Th17 细胞的分化并不是类风湿关节炎患者炎症关节的共同特征。我们得出结论，本文所述的方法可用于对体外分离的 CD4(+) T 细胞中 Th 细胞谱系的分化进行精确分析。
