[PDF][PDF] Cross-regulation of signaling pathways by interferon-γ: implications for immune responses and autoimmune diseases

X Hu, LB Ivashkiv - Immunity, 2009 - cell.com
X Hu, LB Ivashkiv
Immunity, 2009cell.com
Interferon-γ (IFN-γ) is an important mediator of immunity and inflammation that utilizes the
JAK-STAT signaling pathway to activate the STAT1 transcription factor. Many functions of
IFN-γ have been ascribed to direct STAT1-mediated induction of immune effector genes, but
recently it has become clear that key IFN-γ functions are mediated by cross-regulation of
cellular responses to other cytokines and inflammatory factors. Here, we review mechanisms
by which IFN-γ and STAT1 regulate signaling by Toll-like receptors, inflammatory factors …
Interferon-γ (IFN-γ) is an important mediator of immunity and inflammation that utilizes the JAK-STAT signaling pathway to activate the STAT1 transcription factor. Many functions of IFN-γ have been ascribed to direct STAT1-mediated induction of immune effector genes, but recently it has become clear that key IFN-γ functions are mediated by cross-regulation of cellular responses to other cytokines and inflammatory factors. Here, we review mechanisms by which IFN-γ and STAT1 regulate signaling by Toll-like receptors, inflammatory factors, tissue-destructive cytokines, anti-inflammatory cytokines, and cytokines that activate opposing STATs. These signaling mechanisms reveal insights about how IFN-γ regulates macrophage activation, inflammation, tissue remodeling, and helper and regulatory T cell differentiation and how Th1 and Th17 cell responses are integrated in autoimmune diseases.
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