Analysis of tissue macrophage development and its role in vivo

2015 Fiscal Year Final Research Report

• Project/Area Number: 24590584
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Kohyama Masako (香山雅子) 大阪大学, 微生物病研究所, 助教 (70311339)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 組織マクロファージ / 分化

Outline of Final Research Achievements

Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor SPI-C is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. We found that Spic regulated the development of bone marrow macrophages (BMM) and that Spic expression was induced by heme. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor BACH1. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeositasis. Hmox1 (HO-1) is the enzyme that catabolizes free heme into biliverdin, iron, and CO. To analyze the function of RPM in malaria parasite clearance, we infected HO-1 conditional KO mice that lack RPM. Through the analysis of this cKO mice, we found unexpected role of RPM in parasite clearance.

Free Research Field

免疫学