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Immunity. 2009 Oct 16;31(4):539-50. doi: 10.1016/j.immuni.2009.09.002.

Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases.

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Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA.


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.

[Indexed for MEDLINE]
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