| First Author | Libregts SF | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 9 | Pages | 2578-88 |
| PubMed ID | 21725055 | Mgi Jnum | J:176898 |
| Mgi Id | MGI:5293167 | Doi | 10.1182/blood-2010-10-315218 |
| Citation | Libregts SF, et al. (2011) Chronic IFN-alpha production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. Blood 118(9):2578-88 |
| abstractText | Anemia of chronic disease is a complication accompanying many inflammatory diseases. The proinflammatory cytokine IFN-gamma has been implicated in this form of anemia, but the underlying mechanism remains unclear. Here we describe a novel mouse model for anemia of chronic disease, in which enhanced CD27-mediated costimulation strongly increases the formation of IFN-gamma-producing effector T cells, leading to a progressive anemia. We demonstrate that the anemia in these mice is fully dependent on IFN-gamma and that this cytokine reduces both the life span and the formation of red blood cells. Molecular analysis revealed that IFN-gamma induces expression of the transcription factors of interferon regulatory factor-1 (IRF-1) and PU.1 in both murine and human erythroid precursors. We found that, on IFN-gamma stimulation, IRF-1 binds to the promoter of SPI.1 (PU.1) and induces PU.1 expression, leading to inhibition of erythropoiesis. Notably, down-regulation of either IRF-1 or PU.1 expression is sufficient to overcome IFN-gamma-induced inhibition of erythropoiesis. These findings reveal a molecular mechanism by which chronic exposure to IFN-gamma induces anemia. |
