Development of new method for measuring mitochondrial activity of dendritic cells

Research Project

Project/Area Number	16K19196
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Laboratory medicine
Research Institution	Kyushu University
Principal Investigator	Gotoh Kazuhito 九州大学, 大学病院, 助教 (50711214)
Project Period (FY)	2016-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	ミトコンドリア / 敗血症 / 樹状細胞 / 臨床検査 / 細菌
Outline of Final Research Achievements	Sepsis is a major cause of morbidity and mortality in seriously ill patients and mitochondrial dysfunction is associated with poor outcomes in septic patients. We identified p32/C1QBP/HABP1 as a regulator of IL-6 production in response to lipopolysaccharide (LPS). LPS induced IL-6 overproduction in p32 deficient mouse embryonic fibroblasts (MEFs) through activating transcription factor (ATF) 4 dependent pathways. Using a LPS-induced endotoxin shock model, mice with p32 ablation in myeloid cells showed increased lethality and overproduction of IL-6. We constructed new system to measure real-time metabolic activity of dendritic cells. We demonstrated that p32/C1qbp, which functions as a multifunctional chaperone protein of mitochondria, supports not only mitochondrial metabolism but also DC maturation.