Molecular analysis of mast cell activation in mouse models for autoinflammatory syndromes and its use for anti-inflammatory drug development

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290036
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: ABE Koichiro 東海大学, 医学部, 准教授 (90294123)
• Co-Investigator(Kenkyū-buntansha): RA Chisei 日本大学, 医学部, 客員教授 (60230851) ; TAJIMA Atsushi 金沢大学, 医薬保健研究域, 教授 (10396864)
• Co-Investigator(Renkei-kenkyūsha): NUNOMURA Satoshi 佐賀大学, 医学部, 助教 (70424728) ; KIMURA Minoru 東海大学, 医学部, 教授 (10146706)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 病態モデル / 関節炎 / 自然炎症 / 変異マウス

Outline of Final Research Achievements

Autoinflammation syndromes are caused by an exaggerated innate immune system response without autoatibodies and selfreactive T cells, and the patients show spontaneous inflammation affecting multiple organs. The Ali14 and Ali18 are gain-of-function mutations in cell signaling effector enzyme genes, and trigger inflammation through the innate immune cells by unknown mechanisms. Because the double mutant with Ali18 and W/Wv , which lacks mast cell population, did not show autoinflammation, we analyzed cultured mast cells from mutant bone marrow.Ali14 and Ali18 mast cells showed lower calcium concentration for antigen stimulation. Further, micro-array analysis identified 1124 and 750 up-regulated genes specifically in Ali18 and Ali14 mast cells, respectively. Further, 127 genes were up-regulated in both mutant mast cells. Cell signaling pathways involving these up-regulated genes might provide insight into extensive repression against autoinflammation.

Free Research Field

実験動物学