| Budget Amount *help |
¥109,200,000 (Direct Cost: ¥84,000,000、Indirect Cost: ¥25,200,000)
Fiscal Year 2018: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2017: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2016: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2015: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000)
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| Outline of Final Research Achievements |
Sensing tissue damage is a crucial function of pattern recognition receptors (PRRs). However, endogenous ligand recognition by PRRs is not well documented. Macrophage inducible C-type lectin (Mincle) is a PRR that recognizes both pathogens and damaged cells. In this study, we isolated endogenous glycolipids derived from dying cells and identified a ubiquitous intracellular metabolite, β-glucosylceramide (GlcCer), as a Mincle ligand. β-GlcCer induced inflammatory and acquired immune responses via Mincle on myeloid cells. Accumulation of β-GlcCer leads to Gaucher disease, a disorder characterized mainly by systemic inflammation. In a Gaucher model in which mice are deficient in the β-GlcCer-degrading enzyme, further deletion of the Mincle gene attenuated inflammatory responses. These re- sults suggest that β-GlcCer is an endogenous Mincle ligand and acts as an immunostimulatory factor upon cell death.
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