Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.
Interferon-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.
Hu
Xiaoyu
X
Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA.
Ivashkiv
Lionel B
LB
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D011494:Protein Kinases / Q000276:immunology / Q000378:metabolism; D050791:STAT Transcription Factors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D050791:STAT Transcription Factors; D051193:Toll-Like Receptors; D007371:Interferon-gamma; D011494:Protein Kinases