IRF-7: new role in the regulation of genes involved in adaptive immunity

The interferon regulatory factor 7 (IRF-7), a member of the IRF family of transcription factors, is a key player in the innate immune response against viral infections. Constitutive expression of IRF-7 is limited to peripheral blood lymphocytes and dendritic cells while in most cell types its expression can be induced by type I interferon (INF). IRF-7 is sequestered in the cytoplasm of uninfected cells and following viral Infection, double-stranded RNA (dsRNA), or Toll-like Receptor (TLR) signaling, it becomes phosphorylated by TBK and IKK-i kinases. Phosphorylated IRF-7 migrates in the nucleus where it can activate IFN type I genes and other interferon-stimulated genes (ISGs). Here we report that the overexpression of a constitutively active form of IRF-7 binds and positively regulates the transcriptional activity of the promotor of IRF-1 and low molecular mass polypeptide-2 (LMP-2), two proteins that play a key role in adaptive immunity. The so far unrecognized role of IRF-7 in LMP-2 stimulation points to IRF-7 as a transcriptional regulator that bridges innate and adaptive immunity.