ArticlePloS one2017
Re-evaluation of IL-10 signaling reveals novel insights on the contribution of the intracellular domain of the IL-10R2 chain.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Dynamic regulation of the 'mitochondria‑immune axis' in myocardial infarction: Molecular mechanisms driving macrophage polarization through energy metabolism disorders (Review).Molecular medicine reports · 2026Review
- IL-10-STAT3-Dependent Transcriptional Regulation in Microglia: Alzheimer's Disease and Neuroinflammation.Biomedicines · 2026Review
- IL-10's contextual role in cytotoxic antitumor immunity: evidence, controversies, and therapeutic translation.Frontiers in immunology · 2026Review
- Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications.International journal of molecular sciences · 2023Review
- Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Interleukin-10 in cancer immunotherapy: from bench to bedside.Trends in cancer · 2023Review
- Cytokine Imbalance as a Biomarker of Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2022Review
- Parapoxvirus Interleukin-10 Homologues Vary in Their Receptor Binding, Anti-Inflammatory, and Stimulatory Activities.Pathogens (Basel, Switzerland) · 2022Article
- Immune Infiltration-Related ceRNA Network Revealing Potential Biomarkers for Prognosis of Head and Neck Squamous Cell Carcinoma.Disease markers · 2022Article
- A Molecular Analysis of Cytokine Content across Extracellular Vesicles, Secretions, and Intracellular Space from Different Site-Specific Adipose-Derived Stem Cells.International journal of molecular sciences · 2021Article
- Maternal Serum Cytokine Concentrations in Healthy Pregnancy and Preeclampsia.Journal of pregnancy · 2021Review
- Engineering designer beta cells with a CRISPR-Cas9 conjugation platform.Nature communications · 2020Article
- TYK2 in Tumor Immunosurveillance.Cancers · 2020Review
- A multiplex biomarker assay improves the diagnostic performance of HE4 and CA125 in ovarian tumor patients.PloS one · 2020Article
- TheFrontiers in immunology · 2019Article
- Granulocyte-macrophage colony-stimulating factor negatively regulates early IL-10-mediated responses.Future science OA · 2018Article
- The Interleukin-10 Family of Cytokines and Their Role in the CNS.Frontiers in cellular neuroscience · 2018Review
Corrections and comments
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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
Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a key role in maintaining immune homeostasis. IL-10-mediated responses are triggered upon binding to a heterodimeric receptor complex consisting of IL-10 receptor (IL-10R)1 and IL-10R2. Engagement of the IL-10R complex activates the intracellular kinases Jak1 and Tyk2, but the exact roles of IL-10R2 and IL-10R2-associated signaling via Tyk2 remain unclear. To elucidate the contribution of IL-10R2 and its signaling to IL-10 activity, we re-evaluated IL-10-mediated responses on bone marrow-derived dendritic cells, macrophages and mast cells. By using bone marrow from IL-10R-/- mice it was revealed that IL-10-mediated responses depend on both IL-10R1 and IL-10R2 in all three cell types. On the contrary, bone marrow-derived cells from Tyk2-/- mice showed similar responses to IL-10 as wild-type cells, indicating that signaling via this IL-10R2-associated kinase only plays a limited role. Tyk2 was shown to control the amplitude of STAT3 activation and the up-regulation of downstream SOCS3 expression. SOCS3 up-regulation was found to be cell-type dependent and correlated with the lack of early suppression of LPS-induced TNF-α in dendritic cells. Further investigation of the IL-10R complex revealed that both the extracellular and intracellular domains of IL-10R2 influence the conformation of IL-10R1 and that both domains were required for transducing IL-10 signals. This observation highlights a novel role for the intracellular domain of IL-10R2 in the molecular mechanisms of IL-10R activation.
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