IFNL1 gene

The IFNL1 gene (IFNL1 stands for: Interferon Lambda 1 - see below Interferon-lambda) is a protein-coding gene located on chromosome 19q13. An important paralog of this gene is IFNL3.

The IFNL1 gene encodes a cytokine, a type III interferon(interferon-lambda also known as interleukin-29 ) that is distantly related to the type I interferons and the IL-10 family. The IFNL1 gene and the genes encoding interleukin 28A (IL28A) and interleukin 28B (IL28B) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor consisting of the interleukin-10 receptor, beta(IL10RB) and the interleukin-28 receptor, alpha (IL28RA).

The cytokine encoded by the IFNL1 gene, incfereon-lambda, is a cytokine with antiviral, antitumor and immunomodulatory activities. Plays a crucial role in antiviral host defense, especially in epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor, which is composed of IL10RB and IFNLR1. Activation of the receptor leads to activation of the JAK/STAT signaling pathway, resulting in expression of IFN-stimulated genes (ISG) that mediate the antiviral state. Receptor distribution is limited. Therefore, only limited targets exist: These are mainly epithelial cells (mucosa cells). This cell type-selective effect is due to the epithelial cell-specific expression of its receptor IFNLR1. Interferon-lambda exerts an immunomodulatory effect by upregulating the expression of MHC class I antigens.

Diseases associated with IFNL1 include:

• Hypotrichosis, congenital, with juvenile macular dystrophy (OMIM: OMIM: 601553). The disease is characterized by early alopecia and severe degenerative changes in the macula of the retina, leading to blindness in the second to third decade of life. It is caused by an autosomal recessive mutation of the CDH3 gene on chromosome 16q22.1. 8 genes are associated with this complex disease 2 with high evidence (elite gene associations) and 6 non-elite and text-mined gene associations. These include: the IFNLR1 gene, the IFNL2 gene and the IL26 gene.
• viral infectious diseases.

1. Li SF et al. (2017) Interferon-omega: Current status in clinical applications. Int Immunopharmacol 52:253-260.
2. Pan YY et al. (2023) Interferon-lambda: New role in intestinal symptoms of COVID-19. World J Gastroenterol 29: 1942-1954.
3. Wallace JW et al. (2021) Interferon Lambda in the Pathogenesis of Inflammatory Bowel Diseases. Front Immunol 12:767505.
4. Wolf SJ et al. (2022) IFN-κ is critical for normal wound repair and is decreased in diabetic wounds. JCI Insight 7:e152765.