2007 Fiscal Year Final Research Report Summary
Analysis of IL-7 receptor and application for biological protection
| Project/Area Number |
18580309
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | Kyoto University |
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Principal Investigator |
MAKI Kazushige Kyoto University, Institute for Virus Research, Lecturer (10311424)
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| Co-Investigator(Kenkyū-buntansha) |
IKUTA Koichi Kyoto University, Institute for Virus Research, Professor (90193177)
UEDA Masamichi Kyoto University, Institute for Virus Research, Assistant Professor (50115797)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Cytokine / Signal transduction / γδ T cell / Glucocorticold |
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| 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.
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Research Products
(11 results)
