Type III interferon receptor complex (IFNLR)

The Type III interferon receptor complex is a heterodimeric transmembrane receptor composed of the interferon lambda receptor 1 (IFNLR1) and the interleukin 10 receptor subunit beta (IL10RB) (UniProt Q8IU57, Q08334) [1.3.1, 1.3.4]. It serves as the primary signaling mediator for the Type III interferon family, which includes IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 (NIH) [1.3.3, 1.3.5]. Upon ligand binding, the receptor complex recruits and activates Janus kinases, specifically JAK1 and TYK2, which subsequently phosphorylate STAT1 and STAT2 (PubMed PMID: 23348415) [1.3.2, 1.3.4]. These phosphorylated proteins associate with IRF9 to form the ISGF3 transcription factor complex, which translocates to the nucleus to induce the expression of numerous interferon-stimulated genes (ISGs) (NIH) [1.3.3, 1.3.4]. The biological outcome of this signaling is the establishment of a potent antiviral state, along with anti-proliferative and immunomodulatory effects (Wikipedia) [1.3.1, 1.4.1]. A key feature of this receptor complex is its restricted expression pattern, primarily on epithelial cells of the respiratory, gastrointestinal, and reproductive tracts, as well as certain immune cells like neutrophils (PubMed PMID: 32365318) [1.3.1, 1.4.2]. This localization allows for a compartmentalized immune response that protects barrier surfaces without the broad systemic inflammation associated with Type I interferons (NIH) [1.1.3, 1.2.1]. Therapeutically, the receptor is targeted by recombinant or pegylated Type III interferons, such as peginterferon lambda-1a, for the treatment of chronic viral infections like Hepatitis D and C (Eiger BioPharmaceuticals) [1.2.1, 1.4.4]. It is also being investigated for its role in respiratory viral defense and potential applications in autoimmune diseases and oncology (Frontiers in Immunology) [1.2.3, 1.1.1].

Other names

IFN-lambda receptorIL-28 receptorIL-28RIFNLR1/IL10RB complexIL-28RA/IL-10RB complexInterferon lambda receptor

Agonism of the receptor complex to activate the JAK-STAT signaling pathway (specifically JAK1 and TYK2), leading to the phosphorylation of STAT1 and STAT2 and the subsequent induction of interferon-stimulated genes (ISGs) that provide antiviral and immunomodulatory effects.