| First Author | Chang JH | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 5 | Pages | 1241-51 |
| PubMed ID | 19337996 | Mgi Jnum | J:148101 |
| Mgi Id | MGI:3843543 | Doi | 10.1002/eji.200838913 |
| Citation | Chang JH, et al. (2009) IFN-gamma-STAT1 signal regulates the differentiation of inducible Treg: potential role for ROS-mediated apoptosis. Eur J Immunol 39(5):1241-51 |
| abstractText | Regulatory CD4(+) T cells are important for the homeostasis of immune cells, and their absence correlates with autoimmune disorders. However, how the immune system regulates Treg homeostasis remains unclear. We found that IFN-gamma-deficient-mice had more forkhead box P3 (FOXP3(+)) cells than WT mice in all secondary lymphoid organs except the thymus. However, T-bet- or IL-4Ralpha-deficient mice did not show a similar increase. In vitro differentiation studies showed that conversion of naive T cells into FOXP3(+) cells (neo-generated inducible Treg (iTreg)) by TGF-beta was significantly inhibited by IFN-gamma in a STAT-1-dependent manner. Moreover, an in vivo adoptive transfer study showed that inhibition of FOXP3(+) iTreg generation by IFN-gamma was a T-cell autocrine effect. This inhibitory effect of IFN-gamma on iTreg generation was significantly abrogated after N-acetyl-L-cysteine treatment both in vitro and in vivo, indicating that IFN-gamma regulation of iTreg generation is dependent on ROS-mediated apoptosis. Therefore, our results suggest that autocrine IFN-gamma can negatively regulate the neo-generation of FOXP3(+) iTreg through ROS-mediated apoptosis in the periphery. |
