Interleukin-28 receptor (IL-28R) (IL-28R)

The Interleukin-28 receptor (IL-28R) is a heterodimeric cytokine receptor complex essential for mediating the effects of type III interferons, also known as IFN-lambdas. It consists of two distinct subunits: the ligand-specific Interleukin-28 receptor alpha (IL-28RA, also known as IFNLR1) and the shared Interleukin-10 receptor beta (IL-10RB) (UniProt: Q8IU57, Q08334). Upon binding its ligands—IFN-lambda 1 (IL-29), IFN-lambda 2 (IL-28A), and IFN-lambda 3 (IL-28B)—the receptor activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, primarily involving JAK1 and Tyk2 (PubMed: 12483210). This signaling cascade leads to the induction of interferon-stimulated genes (ISGs) that exert potent antiviral, antiproliferative, and immunomodulatory effects (PubMed: 24035152). Unlike the type I interferon receptor, which is ubiquitously expressed, IL-28R expression is largely restricted to epithelial cells of the respiratory, gastrointestinal, and reproductive tracts, as well as certain immune cells (PubMed: 23562325). This restricted distribution makes the IL-28 receptor an attractive therapeutic target for treating viral infections such as Hepatitis C and B, as it offers the potential for localized antiviral activity with significantly fewer systemic side effects than traditional interferon therapies (PubMed: 21930159). Clinical development has focused on agonists like Peginterferon lambda-1a to leverage this specific immune activation for viral clearance (ClinicalTrials.gov: NCT01082146). Beyond viral infections, the receptor is also being investigated for its role in cancer immunotherapy and the management of inflammatory diseases due to its ability to modulate mucosal immunity. The receptor's signaling is also influenced by genetic polymorphisms in the IFNL3/4 region, which serve as important biomarkers for predicting treatment response in patients with chronic hepatitis (PubMed: 19684571).

Other names

Interferon lambda receptorIFNLRIL-28R complexIFN-lambda receptorCytokine receptor class-II member 28IFNLR1/IL10RB complex

Agonism of the receptor complex to trigger the JAK-STAT signaling pathway, inducing the transcription of interferon-stimulated genes (ISGs) that inhibit viral replication and modulate immune responses (PubMed: 12483210).