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

• Published in: PloS one Vol. 15; no. 2; p. e0229042
• Main Authors: Toyoda, Ayano, Kozaki, Toshinori, Ishii, Kazuo, Taniishi, Momoka, Hattori, Makoto, Matsuda, Hiroshi, Yoshida, Tadashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-02-2020; Public Library of Science (PLoS)
• Subjects: Administration, Oral; Analysis; Anergy; Animals; Antigens; Antigens - administration & dosage; Antigens - immunology; Biochemistry; Bioinformatics; Biology and Life Sciences; Biomarkers; Cell growth; Coenzyme A; CpG Islands; Criminal investigation; Cytosine; Deoxyribonucleic acid; DNA; DNA binding proteins; DNA Methylation; Enzymes; Epigenesis, Genetic; Epigenetics; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genomes; Immune Tolerance; Immunological tolerance; In vivo methods and tests; Leucine; Leucine zipper proteins; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Methylation; Mice; Novels; Polypeptides; Proteins; Research and analysis methods; Ribosomal protein L41; Signal Transduction; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thiols; Japan; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229042

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.