TypIIIInterferone

Type III interferons, commonly called interferon lambda (IFN-λ), constitute a distinct family of cytokines with antiviral activity. The human IFN-λ family includes IFN-λ1 (encoded by IFNL1, previously IL-29), IFN-λ2 (IFNL2, IL-28A), IFN-λ3 (IFNL3, IL-28B), and IFN-λ4 (IFNL4). These cytokines are produced by epithelial cells and certain immune cells in response to viral infection. Unlike type I interferons, IFN-λ action is largely restricted to mucosal and epithelial tissues, where receptor expression is most abundant.

The biological effects are mediated through a receptor complex of IFN-λ receptor 1 (IFNLR1, also known as IL-28Rα) and the shared subunit IL-10 receptor β (IL-10RB). Signaling proceeds via JAK1 and TYK2, leading to activation of STAT1 and STAT2 and formation of ISGF3 with IRF9. This drives transcription of interferon-stimulated genes (ISGs) and an antiviral state, particularly at sites exposed to pathogens, with comparatively limited systemic inflammation.

Production and regulation: IFN-λ genes are induced by pattern recognition receptors recognizing viral components and are especially prominent in mucosal tissues. Their activity complements type I interferons, providing local defense with a narrower scope of action.

Clinical relevance: Type III interferons have been explored as therapeutics, including pegylated IFN-λ, in viral infections such as hepatitis C and, more recently, COVID-19. The therapeutic profile in humans suggests reduced systemic side effects relative to type I interferons. Genetic variation at IFNL4, which allows production of IFN-λ4 in some individuals, can influence viral clearance and treatment responses in hepatitis C.