Comprehensive analysis of DNA methylation and gene expression in orally tolerized T cells

T cell anergy is known to be a crucial mechanism for various types of immune tolerance, including oral tolerance. The expression of several anergy-specific genes was reportedly up-regulated in anergic T cells, and played important roles in the cells. However, how the genes were up-regulated has not been understood. In this study, we comprehensively analyzed the altered gene expression and DNA methylation status in T cells tolerized by oral antigen in vivo. Our results showed that many genes were significantly up-regulated in the orally tolerized T cells, and most of the genes found in this study have not been reported previously as anergy related genes; for example, ribosomal protein L41 (FC = 3.54E06, p = 3.70E-09: Fisher's exact test; the same applies hereinafter) and CD52 (FC = 2.18E05, p = 3.44E-06). Furthermore, we showed that the DNA methylation statuses of many genes; for example, enoyl-coenzyme A delta isomerase 3 (FC = 3.62E-01, p = 3.01E-02) and leucine zipper protein 1 (FC = 4.80E-01, p = 3.25E-02), including the ones distinctly expressed in tolerized T cells; for example, latexin (FC = 3.85E03, p = 4.06E-02 for expression; FC = 7.75E-01, p = 4.13E-01 for DNA methylation) and small nuclear ribonucleoprotein polypeptide F (FC = 3.12E04, p = 4.46E-04 for expression; FC = 8.56E-01, p = 5.15E-01 for DNA methylation), changed during tolerization, suggesting that the distinct expression of some genes was epigenetically regulated in the tolerized T cells. This study would contribute to providing a novel clue to the fine understanding of the mechanism for T cell anergy and oral tolerance.