IFN3

Interferon lambda 3 (IFN-λ3), also known as IFNL3 or interleukin 28B (IL28B), is a type III interferon involved in innate antiviral immunity. It is encoded by a gene in the IFN-λ cytokine family, which is predominantly expressed in response to viral infection. IFN-λ3 is produced by several cell types, including dendritic cells and epithelial cells, and acts mainly at mucosal surfaces such as the respiratory, gastrointestinal and hepatic epithelia.

Biologically, IFN-λ3 signals through a heterodimeric receptor composed of IFNLR1 (also called IL28RA) and IL10RB, activating the JAK–STAT pathway and inducing interferon-stimulated genes that inhibit viral replication and modulate immune responses. Compared with type I interferons, type III interferons tend to have a more localized effect and often provoke less systemic inflammation, due to the limited tissue distribution of IFNLR1.

Clinically, genetic variation near the IFNL3 locus was historically linked to differences in spontaneous clearance of hepatitis C virus (HCV) and to responsiveness to interferon-based HCV therapy; this association was important before the widespread use of direct-acting antivirals. Recombinant and pegylated forms of IFN-λ have been investigated as therapeutics for viral infections because of their targeted action and potentially reduced adverse effects. Research continues into IFN-λ3’s roles in antiviral defense, mucosal immunity and inflammatory regulation.