Interferon lambda receptor 1 (IFNLR1) (IFNLR1)

Interferon lambda receptor 1 (IFNLR1) is a high-affinity cytokine receptor subunit that dimerizes with the interleukin-10 receptor subunit beta (IL10RB) to form the functional receptor complex for type III interferons, including IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 (UniProt: P0DP23). Unlike the ubiquitously expressed type I interferon receptors, IFNLR1 expression is largely restricted to epithelial cells in the respiratory, gastrointestinal, and urogenital tracts, as well as hepatocytes and certain immune cells like neutrophils (PMID: 24035236). Upon ligand binding, the receptor activates the JAK-STAT signaling pathway, primarily through JAK1 and TYK2, leading to the nuclear translocation of the ISGF3 complex and the subsequent induction of interferon-stimulated genes (ISGs) that establish a potent antiviral state (PMID: 29164150). This restricted expression pattern makes IFNLR1 an attractive therapeutic target, as it allows for the induction of mucosal immunity with significantly fewer systemic pro-inflammatory side effects compared to type I interferon therapies. Clinical candidates like peginterferon lambda-1a have been investigated for the treatment of chronic viral hepatitis and acute respiratory infections, including COVID-19, where they have demonstrated the ability to reduce viral load and improve clinical outcomes (PMID: 36752162). Beyond viral infections, IFNLR1 plays a critical role in modulating inflammatory responses at mucosal surfaces and is being studied for its potential involvement in the pathogenesis of inflammatory bowel disease and various epithelial-derived cancers.

Other names

Interleukin-28 receptor subunit alphaIL-28 receptor subunit alphaIL28RACytokine receptor family 2 member 12CRF2-12IFN-lambda-R1LICR2

Receptor agonist