Regulatory roles of HIF-1a and glycolysis in autoimmunity

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591454
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Dokkyo Medical University
• Principal Investigator: KOBATA Tetsuji 獨協医科大学, 医学部, 教授 (10205445)
• Co-Investigator(Renkei-kenkyūsha): HASHIGUCHI Masaaki 獨協医科大学, 医学部, 准教授 (20372443) ; KASHIWAKURA Yuji 獨協医科大学, 医学部, 助教 (40382890)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 自己免疫 / HIF-1a / 解糖系

Outline of Final Research Achievements

In order to understand the pathophysiology of HIF-1α/RAG-2–deficient chimeric mice, which develop autoimmunity resembling human systemic erythematosus, we analyzed mice with conditional knock-outs in HIF-1α in B cells and revealed that autoantibody production is regulated by HIF-1α in the very early stages of B cell development and/or HIF-1α in cells other than B cells. Although HIF-1α/RAG-2–deficient chimeric mice have increased regulatory T cells, we found that regulatory T cells less depend on glycolysis and need CD2-mediated down-regulation of pro-apoptotic Bim for their survival.

Free Research Field

免疫学