| Project/Area Number |
15590440
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
SUZUKI Harumi Yamaguchi Univ., Sch.Med., Dept.Microbiology, Associate prof., 医学部, 助教授 (70235985)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Rac / T cell development / selection / bcl-2 / thymus / signal transduction / apoptosis / pro B cell / bc1-2 / アクチン / Rac1 / T細胞 / 分化 / 胸腺 |
|---|
| Research Abstract |
Rac1, one of the Rho family small GTPases has been shown to work as a "molecular switch" in various signal transduction pathways. In order to directly assess the function of Rac1 in T cell development, we introduced dominant negative (dn) Rac1 gene into Pax5-deficient mouse pro-B cells, which can reconstitute T cell development in vivo. Differentiation of GFP positive dnRac1 expressing thymocytes into CD4- and CD8-single positive (SP) cells was severely impaired, indicating that Rac1 is critical in positive selection of thymocytes. Thymocytes expressing dnRac1 demonstrated increased apoptosis against TCR stimulation. In order to study detailed function of Rac1 in TCR signal transduction of DP thymocytes, we utilized DP cell line DPK, which can differentiate into CD4-SP cells upon TCR stimulation in vitro. DPK expressing dn-Rac1 underwent massive apoptosis upon TCR stimulation and resulted in defective differentiation of CD4-SP cells. TCR dependent actin polymerization and upregulation of Bcl-2 transcription were suppressed in dnRac1-DPK. Collectively, these data indicate that Rac1 is critical in positive selection of thymocyte through not only reorganizing actin cytoskeleton, but also preventing TCR-induced apoptosis via Bcl-2 upregulation.
|
