Introduction of CCR-8
CCR-8, also known as cluster of differentiation w198 (CDw198), GPR-CY6 or CKR-L1, is a member of the beta chemokine receptor family, which is supposed to be a seven transmembrane protein similar to G protein-coupled receptors. It is encoded by CCR8 gene (in human), and primarily expressed in T-helper type-2 lymphocytes and peritoneal macrophages. The ligands of CCR-8 have been identified to be I-309 (CCL1), thymus activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta).
|Basic Information of CCR-8|
|Protein Name||C-C chemokine receptor type 8|
|Aliases||CC chemokine receptor CHEMR1, CKR-L1, CMKBRL2, GPRCY6, TER1, CDw198|
|Organism||Homo sapiens (Human)|
Function of CCR-8 Membrane Protein
CCR-8 and its ligands have shown to play a role in regulation of monocyte chemotaxis and thymic cell apoptosis. Specifically, it may be responsible for the proper positioning of activated T cells within the antigenic challenge sites and specialized areas of lymphoid tissues. CCR8 was found to act as a functional endothelial receptor since it mediated endothelial chemotaxis in response to CCL1. CCR8 has also been identified on human umbilical vein endothelial cells (HUVECs) and has been demonstrated to induce angiogenesis when activated by CCL1. This response can be inhibited by monoclonal antibody directed against the extracellular portion of CCR8 as well as by the Gi-protein inhibitor pertussis toxin. CCR-8 is involved in a variety of pathological conditions, such as peritoneal adhesions, asthma, etc. Especially, the CCL1/CCL8-CCR8 axis plays a role in the pathology of various inflammatory diseases. Moreover, CCR-8 alternatively acts as a coreceptor with CD4 for HIV-1 infection. CCR8 also associates with other diseases such as Molluscum Contagiosum and Kaposi Sarcoma.
Fig.1 Schematic representation of the key functional regions of chemokine receptors. (White, 2013)
Application of CCR-8 Membrane Protein in Literature
1. McCully M.L., et al. CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin. J Immunol. 2018, 200(5): 1639-1650. PubMed ID: 29427415
This article suggests that long-lived memory T cells in human skin can be defined by the expression of CCR8.
2. Berenguer J., et al. Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8. J Extracell Vesicles. 2018, 7(1): 1446660. PubMed ID: 29696074
Authors in this group identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18.
3. Zychowska M., et al. Spinal CCL1/CCR8 signaling interplay as a potential therapeutic target - Evidence from a mouse diabetic neuropathy model. Int Immunopharmacol. 2017, 52: 261-271. PubMed ID: 28961489
Authors of this article reveal that CCL1/CCR8 neuronal signaling plays an important role in the development of diabetic neuropathy and the effectiveness of opioids.
4. Barington L., et al. Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding. J Biol Chem. 2016, 291(31): 16208-20. PubMed ID: 27226537
This article focuses on the importance of conserved extracellular disulfide bridges and aromatic residues in extracellular loop 2 (ECL-2) for ligand binding and activation in the chemokine receptor CCR8. Meanwhile, this aromatic cluster can be exploited in future drug development targeting CCR8.
5. Fu Q., et al. Positive intratumoral chemokine (C-C motif) receptor 8 expression predicts high recurrence risk of post-operation clear-cell renal cell carcinoma patients. Oncotarget. 2016, 7(7): 8413-21. PubMed ID: 26716905
This article demonstrated that CCR8 could drive cancer progress through recruiting certain immune cells and can be considered as a practical prognostic marker may help clinicians in decision making and design of clinical studies.
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