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...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have no conflict of interest to declare.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0229042