ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Distinct conformations of the chemokine receptor CCR4 with implications for its targeting in allergy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- The CCL17/CCL22-CCR4 Axis in Pain Pathogenesis: A Comprehensive Review of Immune-Mediated Mechanisms and Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Topical application of a CCL22-binding aptamer suppresses contact allergy.Molecular therapy. Nucleic acids · 2024Article
- C-C motif chemokine ligand 2 regulates prostaglandin synthesis and embryo attachment of the bovine endometrium during implantation.Cell and tissue research · 2024Article
- Epithelial-intrinsic defects in TGFβR signaling drive local allergic inflammation manifesting as eosinophilic esophagitis.Science immunology · 2023Article
- Role of chemokine-like factor 1 as an inflammatory marker in diseases.Frontiers in immunology · 2023Review
- CC Chemokine Receptor 4 (CCR4) as a Possible New Target for Therapy.International journal of molecular sciences · 2022Review
- Skin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- CCR4 as a Therapeutic Target for Cancer Immunotherapy.Cancers · 2021Review
- CCR4 is a prognostic biomarker and correlated with immune infiltrates in head and neck squamous cell carcinoma.Annals of translational medicine · 2021Article
- What does elevated TARC/CCL17 expression tell us about eosinophilic disorders?Seminars in immunopathology · 2021Review
- Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10.International journal of molecular sciences · 2021Article
- A highly efficient method for the production and purification of recombinant human CXCL8.PloS one · 2021Article
- A degradatory fate for CCR4 suggests a primary role in Th2 inflammation.Journal of leukocyte biology · 2020Article
- Regulation of regulatory T cells in cancer.Immunology · 2019Review
- IL-31 plays dual roles in lung inflammation in an OVA-induced murine asthma model.Biology open · 2019Article
- Evidence for the Existence of a CXCL17 Receptor Distinct from GPR35.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.American journal of respiratory cell and molecular biology · 2018Article
- RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Opportunities for therapeutic antibodies directed at G-protein-coupled receptors.Nature reviews. Drug discovery · 2017Review
- Partial Agonist and Biased Signaling Properties of the Synthetic Enantiomers J113863/UCB35625 at Chemokine Receptors CCR2 and CCR5.The Journal of biological chemistry · 2017Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
CC chemokine receptor 4 (CCR4) is expressed by Th2 and regulatory T cells and directs their migration along gradients of the chemokines CCL17 and CCL22. Both chemokines and receptor are upregulated in allergic disease, making CCR4 a therapeutic target for the treatment of allergy. We set out to assess the mechanisms underlying a previous report that CCL22 is a dominant ligand of CCR4, which may have implications for its therapeutic targeting. Human T cells expressing endogenous CCR4 and transfectants engineered to express CCR4 were assessed for receptor function, using assays of calcium release, chemotaxis, receptor endocytosis, and ligand binding. Despite the two ligands having equal potency in calcium flux and chemotaxis assays, CCL22 showed dominance in both receptor endocytosis assays and heterologous competitive binding assays. Using two different CCR4-specific Abs, we showed that CCR4 exists in at least two distinct conformations, which are differentially activated by ligand. A major population is activated by both CCL17 and CCL22, whereas a minor population is activated only by CCL22. Mutation of a single C-terminal residue K310 within a putative CCR4 antagonist binding site ablated activation of CCR4 by CCL17, but not by CCL22, despite having no effect on the binding of either ligand. We conclude that CCL17 and CCL22 are conformationally selective ligands of CCR4 and interact with the receptor by substantially different mechanisms. This finding suggests that the selective blockade of CCR4 in allergy may be feasible when one CCR4 ligand dominates, allowing the inhibition of Th2 signaling via one ligand while sparing regulatory T cell recruitment via another.
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