ArticleProceedings of the National Academy of Sciences of the United States of America2010
IL-27 structural analysis demonstrates similarities with ciliary neurotrophic factor (CNTF) and leads to the identification of antagonistic variants.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Characterization of an isogenicInfection and immunity · 2026Article
- Recent Insights Into Targeting Interleukin-27 in Coronary Artery Disease.Journal of cardiovascular translational research · 2025Review
- Cardiotrophin-like cytokine factor 1 forms a complex with IL12/IL23p40.Scientific reports · 2025Article
- Transcriptomic Analysis of Mayaro Virus-Infected Human Macrophages: Effects on Inflammatory and Antiviral Response.The American journal of tropical medicine and hygiene · 2025Article
- IL-12 family cytokines and autoimmune diseases: A potential therapeutic target?Journal of translational autoimmunity · 2025Review
- Article
- Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency.Nature communications · 2024Article
- Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.Science advances · 2023Article
- Structural insights into the assembly of gp130 family cytokine signaling complexes.Science advances · 2023Article
- American-Asian- and African lineages of Zika virus induce differential pro-inflammatory and Interleukin 27-dependent antiviral responses in human monocytes.Virus research · 2023Article
- Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27.Cell reports · 2022Article
- Structural insights into the assembly and activation of the IL-27 signaling complex.EMBO reports · 2022Article
- Synergistic Effects of Toll-Like Receptor 1/2 and Toll-Like Receptor 3 Signaling Triggering Interleukin 27 Gene Expression in Chikungunya Virus-Infected Macrophages.Frontiers in cell and developmental biology · 2022Article
- IL-30Experimental & molecular medicine · 2021Review
- Case Report: Novel Copy Number Variant 16p11.2 Duplication Associated With Prune Belly Syndrome.Frontiers in pediatrics · 2021Article
- Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its BioactivityMolecular therapy. Methods & clinical development · 2020Article
- A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer.Frontiers in oncology · 2019Review
- Interleukin (IL)-6 Inhibits IL-27- and IL-30-Mediated Inflammatory Responses in Human Monocytes.Frontiers in immunology · 2018Article
- Epstein-Barr virus-induced gene 3 (EBI3) can mediate IL-6The Journal of biological chemistry · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-27, consisting of the subunits IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3), is a heterodimeric cytokine belonging to the IL-6/IL-12 family of cytokines. IL-27p28 is a four-helical cytokine requiring association with the soluble receptor EBI3 to be efficiently secreted and functionally active. Computational and biological analyses of the IL-27 binding site 1 to its receptor revealed important structural proximities with the ciliary neurotrophic factor group of cytokines and highlighted the contribution of p28 Trp(97), as well as of EBI3 Phe(97), Asp(210), and Glu(159), as key residues in the interactions between both cytokine subunits. WSX-1 (IL-27R) and gp130 compose the IL-27 receptor-signaling complex, recruiting the STAT-1 and STAT-3 pathways. A study of IL-27 binding site 3 showed that Trp(197) was crucial for the cytokine's interaction with gp130, but that the mutated cytokine still recognized IL-27R on the cell surface. IL-27 exerts both pro- and anti-inflammatory functions, promoting proliferation and differentiation of Th1 and inhibiting Th17 differentiation. Our results led us to develop mutated forms of human and mouse IL-27 with antagonistic activities. Using an in vivo mouse model of concanavalin A-induced Th1-cell-mediated hepatitis, we showed that the murine IL-27 antagonist W195A decreased liver inflammation by downregulating the synthesis of CXCR3 ligands and several acute phase proteins. Together, these data suggest that IL-27 antagonism could be of interest in down-modulating acute IL-27-driven Th1-cell-mediated immune response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.