Functional crosstalk between type I and II interferon through the regulated expression of STAT1

Daniel J Gough, Nicole L Messina, Linda Hii, Jodee Ann Gould, Kanaga Sabapathy, Ashley P S Robertson, Joseph A Trapani, David E Levy, Paul John Hertzog, Christopher J P Clarke, Ricky W Johnstone

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119 Citations (Scopus)


Autocrine priming of cells by small quantities of constitutively produced type I interferon (IFN) is a well-known phenomenon. In the absence of type I IFN priming, cells display attenuated responses to other cytokines, such as anti-viral protection in response to IFNgamma. This phenomenon was proposed to be because IFNalpha/beta receptor1 (IFNAR1) is a component of the IFNgamma receptor (IFNGR), but our new data are more consistent with a previously proposed model indicating that regulated expression of STAT1 may also play a critical role in the priming process. Initially, we noticed that DNA binding activity of STAT1 was attenuated in c-Jun(-/-) fibroblasts because they expressed lower levels of STAT1 than wild-type cells. However, expression of STAT1 was rescued by culturing c-Jun(-/-) fibroblasts in media conditioned by wild-type fibroblasts suggesting they secreted a STAT1-inducing factor. The STAT1-inducing factor in fibroblast-conditioned media was IFNbeta, as it was inhibited by antibodies to IFNAR1, or when IFNbeta expression was knocked down in wild-type cells. IFNAR1(-/-) fibroblasts, which cannot respond to this priming, also expressed reduced levels of STAT1, which correlated with their poor responses to IFNgamma.
Original languageEnglish
Pages (from-to)1 - 12
Number of pages12
JournalPLoS Biology
Issue number4 (e1000361)
Publication statusPublished - 2010

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