TY - JOUR
T1 - Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate Immunity
AU - Xu, Dakang
AU - Holko, Michelle
AU - Sadler, Anthony J.
AU - Scott, Bernadette
AU - Higashiyama, Shigeki
AU - Berkofsky-Fessler, Windy
AU - McConnell, Melanie J.
AU - Pandolfi, Pier Paolo
AU - Licht, Jonathan D.
AU - Williams, Bryan R.G.
N1 - Funding Information:
We thank K. Fitzgerald for the RASD2-luc constructs, P. Hertzog and P. Fitzgerald-Bocarsly for helpful advice, and N. de Weerd, S. Samarajiwa, and J. Gould for mouse IFNα and SFV virus. We thank I. Harper, S. Firth, and C. Lo (Monash Micro Imaging) for the confocal microscopic analysis and M. Gantier, D. Wang, D. Wu, and J. Ou for technical assistance. We also thank F. Cribbin for critical reading and preparation of the manuscript. This work was supported by grants from the National Health and Medical Research Council of Australia (436814 to B.R.G.W.) and the National Institutes of Health (P01 CA062220 and R01 AI034039 to B.R.G.W.).
PY - 2009/6/19
Y1 - 2009/6/19
N2 - Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an association of PLZF with promyelocytic leukemia protein (PML) and histone deacetylase 1 (HDAC1) to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice had a specific ISG expression defect and as a result were more susceptible to viral infection. This susceptibility correlated with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.
AB - Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an association of PLZF with promyelocytic leukemia protein (PML) and histone deacetylase 1 (HDAC1) to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice had a specific ISG expression defect and as a result were more susceptible to viral infection. This susceptibility correlated with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - https://www.scopus.com/pages/publications/66949167924
U2 - 10.1016/j.immuni.2009.04.013
DO - 10.1016/j.immuni.2009.04.013
M3 - Article
C2 - 19523849
AN - SCOPUS:66949167924
SN - 1074-7613
VL - 30
SP - 802
EP - 816
JO - Immunity
JF - Immunity
IS - 6
ER -