title: Significant role for IRF3 in both T cell and APC effector functions during T cell responses.
abstract: Interferon Regulatory Factor (IRF)3 is a crucial transcription factor during innate immune responses. Here we show IRF3 also has a role in adaptive T cell immune responses. Expression of IFN-γ, IL-17, and Granzyme B (GrB) during in vitro T cell responses was impaired when either dendritic cells (DCs) or T cells were derived from IRF3KO mice. Unexpectedly, IRF3-dependent NK-activating molecule (INAM), which is an NK cell activating factor of the DC innate immune response, was induced during the T cell response. Additionally, supernatants from responding T cells induced ISG54 in the RAW264.7 macrophage cell line in an IRF3 dependent manner. Moreover, addition of anti-IFN-γ prevented supernatant induction of ISG54 and recombinant IFN-γ stimulated ISG54 expression. Thus, IRF3 in APCs and T cells is required for optimal T-cell effector function and the ability of T cells to influence innate immune function of APCs.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, United States.
authors.forename: Zacharey
authors.initials: Z
authors.lastname: Guinn
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, United States.
authors.forename: Anna T
authors.initials: AT
authors.lastname: Lampe
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, United States; Nebraska Center for Virology, University of Nebraska-Lincoln, United States.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Brown
authors.affiliation: Nebraska Center for Virology, University of Nebraska-Lincoln, United States; Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, United States. Electronic address: tpetro@unmc.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000067996:RAW 264.7 Cells; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C000595458:INAM protein, mouse; C522692:ISG54 protein, mouse; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D007371:Interferon-gamma
keywords: Dendritic cells; Granzyme-B; Innate immunity; Interferon Regulatory Factor-3; Interferon stimulated gene-54; Interferon-γ; Interleukin-17; T cells