Analysis of role of PILRalpha in monocyte infiltration and of its physiological significance in vivo

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08531
• 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 (Ise) Masako (香山雅子) 大阪大学, 微生物病研究所, 助教 (40598885)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 単球 / 浸潤 / 肥満

Outline of Final Research Achievements

Paired immunoglobulin-like type 2 receptorα (PILRα) is an inhibitory receptor that is mainly expressed on myeloid cells, and negatively regulates neutrophil infiltration during inflammation. However, its role on monocyte has remained unknown. Under both steady-state and inflammatory conditions, monocytes migrate into tissues and differentiate into macrophages. Macrophages in adipose and liver tissues play important roles in tissue homeostasis and pathogenesis of metabolic diseases. We found that PILRα controls monocyte mobility through regulating integrin signaling and inhibiting CD99-CD99 binding. Moreover, we found that Pilra-/- mice develop obesity and hepatomegaly with fibrosis, and the numbers of macrophages in adipose and liver tissues are significantly increased in Pilra-/- mice. These data suggest that immune inhibitory receptor, PILRα, plays an important role in the prevention of obesity and liver fibrosis.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

現代病とも言えるメタボリックシンドロームに関連する疾患において、疾患局所に浸潤し組織固有の機能を持ったマクロファージに分化する能力を有する単球が注目されている。申請者らはPILRα分子が単球の組織への浸潤を抑制的に制御していることが明らかにした。このことは逆に、脂肪組織あるいは肝臓への単球の浸潤を防ぐことができれば、肥満や肝臓の繊維化を抑制できることを意味している。つまり申請者らによって明らかとなったPILRα分子による単球の動態の制御によって、これらの疾患の予防あるいは治療に繋げられる成果だと考えている。