Significant role for IRF3 in both T cell and APC effector functions during T cell responses

Cell Immunol. 2016 Dec:310:141-149. doi: 10.1016/j.cellimm.2016.08.015. Epub 2016 Sep 4.

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.

Keywords: Dendritic cells; Granzyme-B; Innate immunity; Interferon Regulatory Factor-3; Interferon stimulated gene-54; Interferon-γ; Interleukin-17; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism*
  • Interferon-gamma / metabolism
  • Macrophages / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RAW 264.7 Cells
  • T-Lymphocytes / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • INAM protein, mouse
  • ISG54 protein, mouse
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Membrane Glycoproteins
  • Transcription Factors
  • Interferon-gamma