InterferonStimulated

Interferon-stimulated describes the state or response of cells and genes that occurs after exposure to interferons. It is most often used in reference to interferon-stimulated genes (ISGs), a diverse group of genes upregulated by signaling from type I (IFN-α/β), type II (IFN-γ), or type III (IFN-λ) interferons. Activation of this response helps establish an antiviral state and modulates various aspects of the immune system.

The signaling mechanisms involve cytokine-receptor interactions that trigger the JAK-STAT pathway. Type I and type III interferons activate JAK kinases leading to phosphorylation of STAT1 and STAT2, which form a complex with IRF9 and enter the nucleus to bind ISREs (interferon-stimulated response elements). Type II interferon signals mainly through STAT1 homodimers that bind GAS elements. These transcription factors induce ISG expression, resulting in diverse antiviral and immunomodulatory effects. Well-known ISGs include MX1/2, OAS1-3, PKR (EIF2AK2), IFIT family proteins, IFITM proteins, RSAD2 (viperin), and APOBEC3 enzymes. The collective activity can inhibit viral replication, degrade viral RNA, inhibit viral protein synthesis, enhance antigen presentation, and influence apoptosis and signaling pathways.

Interferon-stimulated responses are central to innate immunity and are leveraged in clinical contexts, such as using interferons to treat certain viral infections and cancers. Dysregulation of interferon signaling and ISG expression is linked to autoimmune diseases and chronic inflammatory states, where a persistent interferon-stimulated gene signature can be observed. In research, measuring ISG expression helps assess the strength and nature of interferon responses and their role in disease.