Abstract
A key function of interferons is priming multiple cell types for enhanced activation by cytokines and inflammatory factors, including tumor necrosis factor, bacterial lipopolysaccharide and interferons themselves. Here we show that interferon-α (IFN-α)–induced activation of the transcriptional activator STAT1 and inflammatory STAT1 target genes was enhanced in IFN-γ-primed macrophages. Enhanced IFN-α signaling and proinflammatory function were dependent on the tyrosine kinase Syk and on adaptor proteins that activate Syk through immunoreceptor tyrosine activation motifs. Increased STAT1 expression contributed to enhanced IFN-α-induced STAT1 activation in primed macrophages. These results identify a mechanism by which crosstalk between cytokine and immune cell–specific immunoreceptor tyrosine activation motif–dependent signaling pathways regulates macrophage responses to IFN-α.
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Acknowledgements
We thank V. Tybulewicz, M. Muller, G. Yap, C. Schindler and L. van Parijs for providing mice, bone marrow cells and plasmids; X. Ma and K. Park-Min for critically reviewing the manuscript; and M. Humphrey and M. Nakamura for discussions. Supported by the National Institutes of Health (L.B.I.), Abbott Scholar Program (I.T.) and Cancer Research Institute (X.H.).
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Tassiulas, I., Hu, X., Ho, H. et al. Amplification of IFN-α-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors. Nat Immunol 5, 1181–1189 (2004). https://doi.org/10.1038/ni1126
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DOI: https://doi.org/10.1038/ni1126
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