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lüll Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases Hu X; Ivashkiv LBImmunity 2009[Oct]; 31 (4): 539-50Interferon-gamma (IFN-gamma) 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-gamma have been ascribed to direct STAT1-mediated induction of immune effector genes, but recently it has become clear that key IFN-gamma functions are mediated by cross-regulation of cellular responses to other cytokines and inflammatory factors. Here, we review mechanisms by which IFN-gamma 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-gamma 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.|Animals[MESH]|Autoimmune Diseases/*immunology/metabolism[MESH]|Cytokines/immunology/metabolism[MESH]|Humans[MESH]|Immunity, Active[MESH]|Immunity, Innate[MESH]|Interferon-gamma/*immunology/metabolism[MESH]|Protein Kinases/immunology/metabolism[MESH]|STAT Transcription Factors/immunology/metabolism[MESH]|Signal Transduction/*immunology[MESH]|T-Lymphocyte Subsets/*immunology/metabolism[MESH]|Toll-Like Receptors/immunology/metabolism[MESH] |