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Open Access Publications from the University of California

A Pathogen Independent T-cell Intrinsic role for IRF3

  • Author(s): Dankar, Amay
  • Advisor(s): David, Michael
  • et al.

IRF3 has been recognized as a crucial transcription factor for the activation of innate immune responses. Recent studies have implicated IRF3 in regulating IL17A production of the CD4+ subset, Th17. Previous results using in vivo models of autoimmune disorders suggest this regulation is necessary for optimal disease induction. Using in vitro culture methods, we further demonstrated the relevance of IRF3 to mouse Th17 cells by co-culturing murine Antigen Presenting cells with purified murine naïve CD4 T cells under Th17 polarizing conditions. We show that IRF3 is required in both Antigen Presenting Cell and CD4 T cells to elicit proper Th17 differentiation independently of antigen presentation. Lastly, we validated an existing Th17 culture method that facilitated Th17 differentiation to better correlate IRF3 with IL17A production in Th17 subsets and provide a robust cytokine cocktail formulation to pinpoint differences in Th17 cell yields in WT vs. IRF3KO cells. Our results demonstrate the multi-faceted role of IRF3 in regulating the immune response within cell subsets and further establish its T-cell intrinsic role.

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