ArticleThe Journal of biological chemistry2012
Novel IL27p28/IL12p40 cytokine suppressed experimental autoimmune uveitis by inhibiting autoreactive Th1/Th17 cells and promoting expansion of regulatory T cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- IL-12 family cytokines and autoimmune diseases: A potential therapeutic target?Journal of translational autoimmunity · 2025Review
- Harnessing IL-27: challenges and potential in cancer immunotherapy.Clinical and experimental medicine · 2025Review
- Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis.Frontiers in immunology · 2025Article
- Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing.Journal of neuroinflammation · 2024Article
- An updated advancement of bifunctional IL-27 in inflammatory autoimmune diseases.Frontiers in immunology · 2024Review
- Circular RNA profile in Graves' disease and potential function of hsa_circ_0090364.Endocrine connections · 2022Article
- Structural insights into the assembly and activation of the IL-27 signaling complex.EMBO reports · 2022Article
- Interleukin‑27 ameliorates allergic asthma by alleviating the lung Th2 inflammatory environment.International journal of molecular medicine · 2022Article
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- The Adverse Effects of Air Pollution on the Eye: A Review.International journal of environmental research and public health · 2022Review
- Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET.Cell chemical biology · 2022Article
- Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level.Journal of clinical medicine · 2021Article
- IL-30Experimental & molecular medicine · 2021Review
- A Chaperone-Like Role for EBI3 in Collaboration With Calnexin Under Inflammatory Conditions.Frontiers in immunology · 2021Review
- Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis.Journal of immunology research · 2021Review
- IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.Cells · 2020Review
- IL‑27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma.International journal of molecular medicine · 2020Article
- Hepatitis B Virus Core Particles Containing a Conserved Region of the G Protein Combined with Interleukin-35 Protected Mice against Respiratory Syncytial Virus Infection without Vaccine-Enhanced Immunopathology.Journal of virology · 2020Article
- Review
- IL-Y Aggravates Murine Chronic Graft-Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
IL-12 family cytokines are important in host immunity. Whereas some members (IL-12, IL-23) play crucial roles in pathogenesis of organ-specific autoimmune diseases by inducing the differentiation of Th1 and Th17 lymphocytes, others (IL-27 and IL-35) suppress inflammatory responses and limit tissue injury induced by these T cell subsets. In this study, we have genetically engineered a novel IL27p28/IL12p40 heterodimeric cytokine (p28/p40) that antagonizes signaling downstream of the gp130 receptor. We investigated whether p28/p40 can be used to ameliorate uveitis, a CNS inflammatory disease. Experimental autoimmune uveitis (EAU) is the mouse model of human uveitis and is mediated by Th1 and Th17 cells. We show here that p28/p40 suppressed EAU by inhibiting the differentiation and inflammatory responses of Th1 and Th17 cells while promoting expansion of IL-10(+)- and Foxp3(+)-expressing regulatory T cells. Lymph node cells from mice treated with p28/p40 blocked adoptive transfer of EAU to naïve syngeneic mice by immunopathogenic T cells and suppressive effects of p28/p40 derived in part from antagonizing STAT1 and STAT3 pathways induced by IL-27 and IL-6. Interestingly, IL27p28 also suppressed EAU, but to a lesser extent than p28/p40. The inhibition of uveitogenic lymphocyte proliferation and suppression of EAU by p28/p40 and IL27p28 establish efficacy of single chain and heterodimeric IL-12 family cytokines in treatment of a CNS autoimmune disease. Creation of the biologically active p28/p40 heterodimeric cytokine represents an important proof-of-concept experiment, suggesting that cytokines comprising unique IL-12 α- and β-subunit pairing may exist in nature and may constitute a new class of therapeutic cytokines.
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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.