Interferon lambda 4 (IFNL4)

Interferon lambda 4 (IFNL4) is a type III interferon and cytokine discovered in humans in 2013, encoded by the IFNL4 gene, which is present or inactive depending on a common polymorphism. Unlike other type III interferons (IFNλ1-3), IFNL4 is often poorly secreted, tends to accumulate inside cells, and structurally interacts with the IFNλR1 and IL-10R2 receptor chains to mediate antiviral and immune responses. Recent evidence also highlights a unique role for IFNL4 as a direct antibacterial protein in the gut, inducing bacterial agglutination and direct killing, which is not observed for other IFNλ family members. Genetic differences in IFNL4 expression have strong effects on host responses to hepatitis C virus and possibly other infections, with expression associated with impaired viral clearance and altered interferon-stimulated gene profiles. IFNL4 signaling activates the JAK-STAT pathway, leading to upregulation of ISGs and modulation of epithelial and mucosal immunity. The molecule presents challenges as a drug target due to secretion issues and complex, sometimes paradoxical, effects on disease outcomes. Notes on ambiguity or issues: IFNL4 is sometimes absent as a functional protein in much of the human population due to a frameshift polymorphism. No small-molecule drugs are currently approved for or known to target IFNL4 directly.

Other names

Interferon lambda-4IFNL4IFN-lambda-4IFNANinterferon lambda-4interferon, lambda 4

Endogenous ligand for IFN lambda receptor complex (IFNλR1/IL-10Rβ), leading to JAK-STAT signaling cascade and induction of antiviral and antibacterial genes