ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2023
Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants.Journal of innate immunity · 2026Article
- Targeting the JAK/STAT pathway in chronic viral infections: opportunities and challenges for immunomodulation.Frontiers in immunology · 2026Review
- Tyrosine kinase 2 inhibitors in the therapy of inflammatory and autoimmune diseases.Pharmacological reports : PR · 2025Review
- Mechanisms of Differential Signal Transduction by IFNLR1 Variants.bioRxiv : the preprint server for biology · 2025Article
- Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated EndogenousJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Single-cell transcriptomics reveals a compartmentalized antiviral interferon response in the nasal epithelium of mice.Journal of virology · 2025Article
- Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- Engineered chimeric receptors for dissecting interferon signaling.Journal of virology · 2024Review
- The Interferon-Lambda Family Celebrates 20 Years of Scientific Discovery.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Type III interferons (IFN-λ) are central to host defense against viral infection of epithelial barrier surfaces. IFN-λ binding to its receptor induces a JAK-STAT cascade through kinases Janus-associated kinase 1 (JAK1) and tyrosine kinase 2 (TYK2), which are associated on either subunit of the heterodimeric type III IFN receptor. Recent studies have shown that TYK2 is not necessary for IFN-λ to signal, in contrast to IFN-α, which uses the same JAK-STAT pathway activated by the type I IFN receptor. The mechanism for this differential TYK2 requirement is unknown. Our study uses synthetic IFN receptors in TYK2-deficient U2OS epithelial cells to define the processes in type I and III IFN signaling that require TYK2. We find that TYK2 deficiency reduces signaling equally from heterodimers of either type I or III IFN receptor intracellular domains. In contrast, JAK1-associated homodimers of IFNAR2 or IFNLR1 are both fully signaling competent even in the absence of TYK2. These results suggest that heterodimerization of the type III IFN receptor is insufficient to confer TYK2-independent signaling. Thus, we propose that noncanonical receptor complexes may participate in endogenous type III IFN signaling to confer TYK2-independent signaling downstream of IFN-λ stimulation.
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