| Project/Area Number |
17390313
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | Kyorin University |
|---|
Principal Investigator |
SHIOHARA Tetuso Kyorin University, School of Medicine, Professor, 医学部, 教授 (10118953)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIZUKAWA Yoshiko Kyorin University, School of Medicine, Instructor, 医学部, 助手 (50301479)
TAKAHASHI Ryo Kyorin University, School of Medicine, Instructor, 医学部, 助手 (00317091)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥12,500,000 (Direct Cost: ¥12,500,000)
|
|---|
| Keywords | fucosyltransferase / skin-homing / virus / E-selectin ligand / CLA / memory T cell / cytokine / Regulatory T cells / regulatory T cell / 薬剤性過敏症症候群 / FucT-VII / Eセクレチンリガンド / エフェクター・メモリーT細胞 |
|---|
| Research Abstract |
We investigated how fucosyltransferase IV and VII (FucT-IV and FucT-VII), which represent the leading enzymes to generate the epitope of E-selectin binding sites could be regulated one another for controlling skin-directed migration of memory CD4^+ or CD8^+ T cells expanded during viral infections.
1. We initially examined how the expression of FucT-IV and VII in the skin-homing T cells can be regulated one another during the differentiation process from naive T cells to memory T cells. Our findings are consistent with the progressive differentiation model, in which skin-homing CD4^+ T cells proceed along a linear differentiation pathway from early activated FucT-IV4 FucT-VIIV+ E-selectin ligand (ESL)V+ CLA to pre-terminally differentiated FucT-IV FucT-VII^+ ESL^+ CLA cells.
2. We nest investigated whether a cytokine milieu, where T cells are activated, could affect the differentiation pathway. Our findings indicate that expression of FucT-IV and FucT-VII can be maintained when the CD4^+
… More
T cell is activated in either IL-4-rich or IL-12-rich milieu and that down-regulation of FucT-IV can be induced when the cell is rested in an IL-12-rich milieu, resulting in the shift from the FucT-IV-dependent phenotype (ESL^+CLA^+) to FucT-VII-dependent phenotype (ESL^+CLA^+). Inversely, when the cell is rested in an IL-4-rich milieu, the shift does not occur : skin-homing T cells do not undergo further differentiation. These results suggest that virus-specific skin-homing T cells expanded during viral infections can acquire the capacity to migrate into the skin through the down-regulation of FucT-IV.
3. We also demonstrated that FoxP3^+ regulatory T cells (Tregs) with the skin-homing phenotype (ESL^<++>CLA^+) and suppressive functions are expanded during the acute phase of drug-induced hypersensitivity syndrome (DIHS) associated with viral reactivations. Most of the Tregs are found to preferentially express FucT-VII, while in other severe drug eruptions not associated with viral reactivations, most of Tregs do not express FucT-VII. In conclusion, the severity of skin lesions in viral infections varies considerably depending on their balance between FucT-IV and FucT-VII expressed in the virus-specific skin-homing T cells and on the extent of expansion of Treg. Less
|
