The regulation of cytokine production by phospholipid on MVB

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Sasai Miwa 大阪大学, 微生物病研究所, 助教 (30631551)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: TLR / IFN / trafficking

Outline of Final Research Achievements

Recent studies indicate that signals from these TLRs bifurcate at the level of distinct endosomal compartments to mediate the induction of cytokine and type I interferon (IFN) genes. TLR9 mediates signals for cytokines from VAMP3+ endosome, and induces IFN genes from LAMP2+ endosome. Phosphoinositides mark distinct subcellular membranes and control membrane trafficking. However, their role in TLR trafficking and signaling remains unclear. Here, we examined the role of phosphatidylinositol 3P 5-kinase, PIKfyve, in TLR trafficking and signaling. We demonstrate that inhibition of PIKfyve activity preferentially blocks TLR9 signaling for type I IFN induction in pDCs. By confocal microscopy, we show that trafficking of both TLR9 and CpG to the LAMP1+ compartment is blocked by PIKfyve inhibitor treatment. These data indicate that PIKfyve provides critical phosphoinositides necessary for the formation of endosome from which TLR9 signals to induce type I IFNs.

Free Research Field

免疫学