| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Dendritic cells (DCs) are critical for linking innate and adaptive immunity. This function is mainly mediated by a group of type I transmembrane proteins, Toll-like receptors (TLRs). In this study, function and signaling mechanisms of TLRs have been clarified as follows.
1. TLR7 can recognize antiviral chemical compounds and virus-derived single stranded RNAs. TLR7 ligand can difirentially activate DC subsets. Furthermore, a TLR9 ligand, CpG DNA, can also stimulate DCs in a subset-dependent manner.
2. LPS can activate DCs through production of interferon-beta (IFN-β). There are five intracytoplasmic adapters that can associate with TLRs, including MyD88,TIRAP/MAL, TRIF, TRAM, and SARM. This IFN-β induction does not depend on MyD88 or TIRAP/MAL but on TRIF and TRAM. Furthermore, TLR4 signaling can enhance Th1 cell supporting ability of DCs through MyD88 and can also activate Th2 cell supporting ability in a MyD88-independent manner.
3. Double stranded RNAS can activate TLR3 signaling through TRIF, but not through TRAM or MyD88.
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