A unique DNA methylation signature defines a population of IFN-/IL-4 double-positive T cells during helminth infection

作者：Deaton Aimee M; Cook Peter C; De Sousa Dina; Phythian Adams Alexander T; Bird Adrian; MacDonald Andrew S^*

来源：European Journal of Immunology, 2014, 44(6): 1835-1841.

DOI：10.1002/eji.201344098

• DNA methylation
• Gata3
• Helminth
• Th1/Th2

Th1 and Th2 cell fates are traditionally viewed as mutually exclusive, but recent work suggests that these lineages may be more plastic than previously thought. When isolating splenic CD4+ T cells from mice infected with the parasitic helminth Schistosoma mansoni, we observed a defined population of IFN-/IL-4 double-positive cells. These IFN-+IL-4+ cells showed differences in DNA methylation at the Ifng and Il4 loci when compared with IFN-+IL-4- (Th1) and IFN--IL-4+ (Th2) cells, demonstrating that they represent a distinct effector cell population. IFN-+IL-4+ cells also displayed a discrete DNA methylation pattern at a CpG island within the body of the Gata3 gene, which encodes the master regulator of Th2 identity. DNA methylation at this region correlated with decreased Gata3 levels, suggesting a possible role in controlling Gata3 expression. These data provide important insight into the molecular mechanisms behind the co-existence of Th1 and Th2 characteristics.

• 出版日期2014-6