| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
The IL-7R plays an essential role in γδ T cell development by inducing V-I recombination of the TCRγ locus through STAT5. Although the tyrosine residues in the intracellular domain of the mouse IL-7Rα chain (IL-7Rα) have been implicated in STAT5 activation, it is still enigmatic whether the residues are essential for γδ T cell development. In this study, we revealed that the tyrosine residues of IL-7Rα are dispensable for γδ T cell development, because the mutant IL-7Rα with four intracellular tyrosine residues replaced with phenylalanine (IL-7R-FFFF) partially rescued yd T cell development from IL-7Rα^<-/-> progenitors. We found that 4R/7R-FFFF induced TCRγ germline transcription and STAT5 activation. In addition, we found that the treatment with MEK1/2 inhibitor decreased the levels of TCRγ germline transcription and STAT5 tyrosine phosphorylation by 4R/7R-FFFF, suggesting that MEK1/2 plays an alternative role in STAT5 activation by IL-7R.
Expression of the IL-7Rα is strictly regulated during development and maturation of lymphocytes. While T cells express the IL-7Rα in the periphery, B cells do not. Although GCs induce the transcription of IL-7Rα gene in T cells, their effect on B cells is largely unknown. We found that GCs induce the transcription and expression of IL-7Rα in mouse peripheral B cells. This effect does not require de novo protein synthesis, because a protein synthesis inhibitor, cycloheximide, does not block the transcription. IL-7R signal pathway is intact in peripheral B cells because Stat5, one of the signal molecules of the IL-7Rα, is phosphorylated by IL-7 stimulation. Furthermore, GC-induced IL-7Rα can transmit survival signal in B cells. Therefore, this study demonstrates that GCs induce the transcription and expression of functional IL-7Rα in peripheral B cells, and implies a potential role of the IL-7R in survival of B cells.
|
