IFNL1 (interferon lambda 1) is a type III interferon cytokine that plays a critical role in antiviral host defense, predominantly in epithelial tissues 1. It functions as a ligand for a heterodimeric receptor composed of IL10RB and IFNLR1, activating JAK/STAT signaling pathways that trigger expression of interferon-stimulated genes (ISGs) to establish antiviral states 2. The restricted epithelial cell-specific expression of IFNLR1 results in IFNL1's selective activity in epithelial tissues and immune cells 3. IFNL1 also upregulates MHC class I antigen expression and promotes regulatory T cell differentiation, demonstrating immunomodulatory effects 2. Clinically, IFNL1 expression is selectively upregulated in alveolar macrophages during Mycobacterium tuberculosis infection compared to monocyte-derived macrophages 4. Recent studies reveal that IFNL1 cooperates with autophagy machinery to mediate autophagic degradation of multiple viral proteins 5, and the IFNL1 rs30461 polymorphism associates with increased COVID-19 severity risk 6. Engineered probiotics expressing IFNL1 demonstrate therapeutic potential in inflammatory bowel disease models by reducing pro-inflammatory cytokines and protecting epithelial barrier integrity 2.