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.
Sgarbanti
Marco
M
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Marsili
Giulia
G
Remoli
Anna Lisa
AL
Orsatti
Roberto
R
Battistini
Angela
A
D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007110:Immunity, Active / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis / Q000235:genetics; D050839:Interferon Regulatory Factor-7 / Q000502:physiology*
D050856:Interferon Regulatory Factor-1; D050839:Interferon Regulatory Factor-7; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases