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

2014 Fiscal Year Final Research Report

• 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
• 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

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.

Free Research Field

消化器病学