| Project/Area Number |
16590570
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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 |
Gastroenterology
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| Research Institution | Hirosaki University |
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Principal Investigator |
ITOH Jugoh Hirosaki University, School of Medicine, Lecturer, 医学部, 講師 (10333717)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOYAMA Tadashi Hirosaki University, University Hospital, Lecturer, 医学部附属病院, 講師 (50312492)
高畑 武功 弘前大学, 医学部附属病院, 助手 (20333726)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | mucosal immunity / CD25^+CD4^+ T cells / signal transduction / mucosal T cells / CD25^+CD4^+ T細胞 |
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| Research Abstract |
Natures of mucosal T cells are tolerant to normal luminal flora and dietary antigens to maintain the intestinal homeostasis. To clarify the mechanisms of the local tolerance, we investigated the involvement of CD25^+CD4^+ regulatory T cells in the hyporesponsiveness of mucosal T cells to the stimulation via T cell receptor (TCR). We already revealed that the CD3 activation- dependent pattern of tyrosine phosphorylation of LPT was markedly reduced compared to that of peripheral blood T cells (PBT). Therefore, we eliminated the regulatory T cells from lamina propria T cells (LPT). However, the pattern of tyrosine phosphorylation of LPT after CD3 stimulation remained still reduced. The result suggested that the hyporesponsiveness of mucosal T cells to the stimulation via TCR might belong to its fundamental nature.
Then, we investigated the MAPK cascade, which was thought to be important after TCR activation. The comparable amounts of MAPK protein were detected both in PBT and LPT. After CD3 stimulation, phosphorylated MAPK was increased both in PBT and LPT. These results indicated that decreased pattern of tyrosine phosphorylation in the up-stream TCR signaling molecules did not affect the MAPK cascade, and the PLCy1 or PKC cascade might be more important.
Tyrosine phosphatases are also important in TCR-mediated activation. Next, we investigated the expression of SHP-1 and SHP-2 proteins. SHP-2 was expressed to the same extent both in PBT and LPT. Although SHP-1 was expressed in both PBT and LPT, two smaller sized molecules of SHP-1 were expressed only in LPT. If the SHP-1 protein in LPT also had been altered in its function, it might be an important clue to explain the hyporesponsiveness of LPT after TCR activation. Further investigation should be necessary to address the role of SHP-1 in LPT.
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