DNA methylation profiles of CD4+ effector memory T cells show distinct differences between Crohn's disease and ulcerative colitis

Research Project

Project/Area Number	24790677
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	Tohoku University
Principal Investigator	SHIGA Hisashi 東北大学, 大学病院, 特任助手 (20583355)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	エピゲノム / クローン病 / アポトーシス / バイサルフェート / 潰瘍性大腸炎 / 炎症性腸疾患 / DNAメチル化 / 脱メチル化剤 / エピジェネティクス / bax
Outline of Final Research Achievements	The comprehensive DNA methylation analysis comparing CD4+ effector memory T cell (Tem) from patients with CD and UC revealed significant differences in 2169 genes (gene-wise analysis), of which 1450 and 719 genes showed hypermethylation in CD- and UC-derived Tem, respectively. In pathway analysis, genes associated with T-cell receptor signaling, helper T-cell differentiation, and death receptor signaling were significantly more common. Furthermore, apoptosis resistance in Tem in CD was eliminated with 5-AZA-induced demethylation. Here we clarified following three points: (1) Differences in DNA methylation in Tem in CD and UC were confirmed. (2) The characteristic biological processes and signaling pathways were identified based on the list of genes exhibiting the difference. (3) Apoptosis susceptibility was suggested to be regulated by DNA methylation.