Click on one of the buttons below to see the signaling pathways that are activated by members of either the type I or type III interferon families.
IFN-gamma is the only type II interferon. While it does not share structural homology or a common receptor with the type I IFNs, it too has antiviral and immunomodulatory properties. The biologically active form of IFN-gamma is a noncovalently-linked homodimer. This homodimer binds to the extracellular domain of two IFN-gamma R1/CD119 chains, which interact with IFN-gamma R2 to form the functional IFN-gamma receptor complex. The IFN-gamma R1 subunits of the receptor complex are associated with Jak1, while the IFN-gamma R2 subunits are associated with Jak2. Activation of Jak1 and Jak2 results in phosphorylation of the receptor and subsequent recruitment and phosphorylation of STAT1. STAT1 phosphorylation leads to its homodimerization and nuclear translocation. Once in the nucleus, STAT1 homodimers bind to IFN-gamma-activated sequence (GAS) elements in the promoters of target genes to regulate their transcription. Many of the target genes that are induced by IFN-gamma/STAT1 signaling are transcription factors that then drive the expression of secondary response genes. In addition, IFN-gamma signaling can activate MAPK, PI 3-K-Akt, and NF-kappa B signaling pathways to regulate the expression of a number of other genes. IFN-gamma signaling plays a key role in host defense by promoting macrophage activation, upregulating the expression of antigen processing and presentation molecules, driving the development and activation of Th1 cells, enhancing natural killer cell activity, regulating B cell functions, and inducing the production of chemokines that promote effector cell trafficking to sites of inflammation. While IFN-gamma has historically been known for its cytotoxic, cytostatic, and anti-tumor properties, multiple studies have also suggested that IFN-gamma may also have context-dependent proliferative and pro-tumorigenic effects.
To learn more, please visit our IL-10/Interferon Family Research Area page