| Autor: |
Rowbotham NJ; Immunobiology Unit, UCL Institute of Child Health, London, United Kingdom., Furmanski AL, Hager-Theodorides AL, Ross SE, Drakopoulou E, Koufaris C, Outram SV, Crompton T |
| Jazyk: |
angličtina |
| Zdroj: |
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2008 Apr 01; Vol. 7 (7), pp. 904-8. Date of Electronic Publication: 2008 Jan 18. |
| DOI: |
10.4161/cc.7.7.5628 |
| Abstrakt: |
Hedgehog proteins signal for differentiation, survival and proliferation of the earliest thymocyte progenitors, but their functions at later stages of thymocyte development and in peripheral T-cell function are controversial. Here we show that repression of Hedgehog (Hh) pathway activation in T-lineage cells, by expression of a transgenic repressor form of Gli2 (Gli2DeltaC2), increased T-cell differentiation and activation in response to TCR signalling. Expression of the Gli2DeltaC2 transgene increased differentiation from CD4(+)CD8(+) to single positive thymocyte, and increased peripheral T cell populations. Gli2DeltaC2 T-cells were hyper-responsive to activation by ligation of CD3 and CD28: they expressed cell surface activation markers CD69 and CD25 more quickly, and proliferated more than wild-type T-cells. These data show that Hedgehog pathway activation in thymocytes and T-cells negatively regulates TCR-dependent differentiation and proliferation. Thus, as negative regulators of TCR-dependent events, Hh proteins provide an environmental influence on T-cell fate. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
