| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
I have analyzed the molecular mechanism on differentiation and activation of innate immune cells including NK or dendritic cells.
1. Mutant mice lacking a transcription factor, C/EBP-γ, exhibited neonatal death due to unknown reasons. Therefore, to analyze C/EBP-γ-deficient immune cells, bone marrow chimeric mice were established and analyzed through the transfer of neonatal splenocytes. In C/EBP-γ-/- chimera, development and function of B and T cells were normal and NK cell numbers were also normal. However, NK cell function such as cytotoxic activity and IFN-γ production was severely impaired in the absence of C/EBP-γ. Notably, NK cell dysfunction was observed in splenic, but not hepatic, NK cells. These results suggest that C/EBP-γ is essential for splenic NK cell function.
2. Toll-like receptor (TLR) signaling can induce maturation of dendritic cells (DCs). A cytoplasmice adaptor, MyD88, associates with TLRs and essential for TLR-induced cytokine induction. Analysis of MyD88-deficient mice revealed the MyD88-independent NF-κB activation in response to TLR4 signaling. MyD88-deficient DCs could enhance surface expression of costimulatory molecules and T cell stimulatory activity in response to LPS, indicating that the MyD88-independent path way can lead to DC maturation, Interestingly, MyD88-deficient DCs did not mature through TLR4 signaling. Taken together, each TLR family member can activate different signaling cascades to exert its biological effects.
|
