Regulation of immune cells by heme and its receptors Bach1 and Bach2

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390066
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: IGARAHI KAZUHIKO 東北大学, 医学(系)研究科(研究院), 教授 (00250738)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ヘム / 免疫 / Bリンパ球 / マクロファージ / 転写因子

Outline of Final Research Achievements

Based on our recent findings that Bach1 and Bach2 are critical regulators of immune cells and that they are receptors of heme, we have tried to investigate the possible regulation of immune cells by heme. First, we established a system to express and to purify hemopexin from HeLa cells. Using a complex of the recombinant hemopexin and heme, we showed that hemopexin-bound heme regulates the protein level of Bach1. Therefore, heme within the blood can affect gene expression by altering the function of Bach1 and possibly Bach2. Using extensive gene expression profiling and chromatin immunoprecipitation-sequencing analysis, we identified candidate target genes of Bach2 in pro-B cells. The list included genes involved in cell cycle regulation, apoptosis, cytokine and chemokines and their receptors, and iron-related genes. We also found a critical function of Bach1 in the regulation of iron-metabolizing macrophages.

Free Research Field

医歯薬学