Abstract
The use of murine systems to model pathogen-induced human diseases presumes that general immune mechanisms between these species are conserved. One important immunoregulatory mechanism involves linkage of innate and adaptive immunity to direct the development of T helper subsets, for example toward subset 1 (TH1) development through STAT4 activation. In analyzing type I interferon signaling, we uncovered a difference between murine and human cells which may affect how these two species control linkage between innate and adaptive immunity. We show that in humans, type I interferons induce TH1 development and can activate STAT4 by recruitment to the IFN-α receptor complex specifically via the carboxy-terminus of STAT2. However, the mouse Stat2 gene harbors a minisatellite insertion that has altered the carboxy-terminus and selectively disrupted its capacity to activate STAT4, but not other STATs. This defect in murine Stat2 suggests that the signals leading to STAT4 activation and TH1 development in CD4+ T cells are different between mice and humans.
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Acknowledgements
We thank Dominic Fenoglio for help with Cell Sorting and Alice Mui for a partial murine Stat2 cDNA. This work was supported by NIH grants AI34580, and HL56419. K.M.M. is an Associate Investigator of the Howard Hughes Medical Institute.
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Farrar, J., Smith, J., Murphy, T. et al. Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse Stat2. Nat Immunol 1, 65–69 (2000). https://doi.org/10.1038/76932
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DOI: https://doi.org/10.1038/76932
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