| First Author | Ben-Shoshan J | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 9 | Pages | 2412-8 |
| PubMed ID | 18792019 | Mgi Jnum | J:141235 |
| Mgi Id | MGI:3817800 | Doi | 10.1002/eji.200838318 |
| Citation | Ben-Shoshan J, et al. (2008) Hypoxia controls CD4+CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. Eur J Immunol 38(9):2412-8 |
| abstractText | Recent data suggest that hypoxia and its principal molecular signature HIF-1 (hypoxia-inducing factor-1) may tune down inflammation by dictating anti-inflammatory programs. We tested the effects of hypoxia and HIF-1alpha on the homeostasis of naturally occurring regulatory T cells (Treg) and their transcriptional activator Foxp3. Hypoxia induced a time-dependent increase in HIF-1alpha in mouse and human T cells. Hypoxia upregulated the expression of Foxp3 in Jurkat T cells, human and murine mononuclear cells. The effects of hypoxia on Foxp3 expression were HIF-1alpha-dependent as they were abolished upon transfection with short-interfering RNAs for HIF-1alpha and promoted by HIF-1alpha overexpression. Hypoxia increased the potency of Treg, as hypoxic CD4(+)CD25(+) lymphocytes were more effective than normoxic cells in suppressing the proliferation of CD4(+)CD25(-) effectors. In vivo expression of HIF-1alpha achieved by hydrodynamic injection of the respective naked DNA similarly induced an increase in Foxp3 expression and an increase in the number of functionally active Foxp3(+)CD4(+)CD25(+) Treg. Thus, hypoxia dictates an anti-inflammatory program by driving expression of HIF-1alpha that acts to increase the number and suppressive properties of naturally occurring CD4(+)CD25(+) Treg. |
