| First Author | Fanzo JC | Year | 2003 |
| Journal | J Exp Med | Volume | 197 |
| Issue | 3 | Pages | 303-14 |
| PubMed ID | 12566414 | Mgi Jnum | J:109285 |
| Mgi Id | MGI:3628674 | Doi | 10.1084/jem.20020717 |
| Citation | Fanzo JC, et al. (2003) Regulation of lymphocyte apoptosis by interferon regulatory factor 4 (IRF-4). J Exp Med 197(3):303-14 |
| abstractText | To ensure that homeostasis of the immune system is maintained, the sensitivity of lymphocytes to Fas-mediated apoptosis is differentially regulated during their activation. The molecular mechanisms that link the activation program of lymphocytes to changes in sensitivity to Fas-mediated apoptosis have, however, not been fully characterized. In these studies, we have investigated whether Fas-mediated apoptosis can be regulated by interferon regulatory factor 4 (IRF-4), a lymphoid-restricted member of the IRF family of transcription factors. IRF-4 expression is upregulated during lymphocyte activation and IRF-4-deficient mice have defects in both lymphocyte activation and homeostasis. Here, we show that stable expression of IRF-4 in a human lymphoid cell line that normally lacks IRF-4 leads to a significantly enhanced apoptotic response on Fas receptor engagement. A systematic examination of the downstream effectors of Fas signaling in IRF-4-transfected cells demonstrates an increased activation of caspase-8, as well as an increase in Fas receptor polarization. We demonstrate that IRF-4-deficient mice display defects in activation-induced cell death, as well as superantigen-induced deletion, and that these defects are accompanied by impairments in Fas receptor polarization. These data suggest that IRF-4, by modulating the efficiency of the Fas-mediated death signal, is a novel participant in the regulation of lymphoid cell apoptosis. |
