Interferon lambda receptor complex (IFNLR)

The Interferon lambda receptor complex is a heterodimeric transmembrane receptor composed of the specific Interferon lambda receptor 1 (IFNLR1) subunit and the shared Interleukin 10 receptor subunit beta (IL10RB) (UniProt: Q8IU57, Q08334). It serves as the primary mediator for Type III interferons (IFN-λ1, -λ2, -λ3, and -λ4), which are critical components of the innate immune system's antiviral defense, particularly at mucosal barriers (NCBI: PMC7154358). Upon ligand binding, the receptor activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, specifically involving JAK1 and TYK2, to induce a suite of interferon-stimulated genes (PubMed: 24035152). Unlike the ubiquitously expressed Type I interferon receptors, the expression of the interferon lambda receptor is largely restricted to epithelial cells and certain immune cell subsets, providing a more localized and less systemic inflammatory response (Nature Reviews Immunology: 10.1038/s41577-019-0170-z). This tissue-specific distribution makes it an attractive therapeutic target for treating viral infections of the respiratory and gastrointestinal tracts, such as Hepatitis C, Hepatitis D, and COVID-19, with potentially fewer systemic side effects than Type I interferon therapies (PubMed: 33547003). Additionally, the receptor plays roles in modulating the immune environment in cancer and autoimmune conditions like systemic lupus erythematosus.

Other names

Type III interferon receptorIL-28 receptorIFN-lambda-R1/IL-10R2 complexIL28RA/IL10RB complexInterferon lambda receptor 1/Interleukin-10 receptor subunit beta complex

Agonism of the receptor complex triggers the JAK-STAT signaling pathway (specifically involving JAK1 and TYK2), inducing the expression of interferon-stimulated genes (ISGs) that establish an antiviral state and modulate immune activity (PubMed: 24035152).