CCR4 Antibodies

Background

The CCR4 gene encodes a cell membrane protein belonging to the G protein-coupled receptor family and is mainly expressed on the surface of lymphocytes. This protein participates in the directed migration of immune cells by specifically binding to chemokines (such as CCL17 and CCL22), playing a key role in inflammatory responses and immune regulation. In 2001, the team led by Japanese scholar Yoshie first clarified its immune function. The research found that the deletion of this gene would lead to abnormal T cell migration, triggering autoimmune diseases or allergic reactions. Its unique seven-time transmembrane domain has become an important target for the development of immunotherapy drugs, and related research has greatly promoted the understanding of the mechanisms of Th2-related diseases such as asthma and atopic dermatitis.

Structure Function Application Advantage Our Products

Structure of CCR4

CCR4 is a G protein-coupled receptor with a molecular weight of approximately 41 kDa, and its molecular weight fluctuates slightly among different mammals due to differences in the degree of glycosylation.

Species	Human	Mouse	Rat	Rhesus monkey
Molecular Weight (kDa)	41	40.5	40.8	41.2
Primary Structural Differences	Containing 355 amino acids, the N-terminal domain mediates ligand recognition	78% homology with human	Intracellular area structure highly conservative	95% homology with human sequence

This protein is composed of 355 amino acids and forms a typical seven-transmembrane topological structure. Its N-terminal extracellular domain contains multiple glycosylation sites, which are responsible for specific binding to chemokines such as CCL17 and CCL22. The three intracellular loops and the C-terminal together form the G protein-coupled region, which mediates downstream signal transduction through Gai proteins. The acidic amino acid cluster on the second extracellular ring is the key site for ligand binding, while the conserved DRY motif in the third transmembrane region maintains the basic activity state of the receptor.

Fig. 1 CCR4—mechanisms of action, possible roles, cellular expression, and disease connections.¹

Key structural properties of CCR4:

Typical configuration of the seven-fold transmembrane helix topology
Extracellular N-terminal domains mediate ligand-specific recognition
Conserved DRY motifs maintain receptor signal transduction functions

Functions of CCR4

The main function of CCR4 is to mediate the migration of immune cells and inflammatory responses, and it also participates in multiple immune regulatory processes.

Function	Description
Chemotaxis of immune cells	By recognizing chemokines such as CCL17 and CCL22, Th2 cells and Treg cells are guided to migrate directively to the inflammatory site.
Regulation of immune homeostasis	Participate in T cells in the thymus of the selection and development, to maintain their own immune tolerance.
Amplification of inflammatory response	Promote the aggregation of inflammatory cells such as eosinophils at the lesion site and aggravate allergic reactions.
Shaping of the tumor microenvironment	Assist tumor-associated T cells in infiltrating tumor tissues and affect the efficacy of tumor immunotherapy.
Pathogen defense	Guide immune cells to the infection site and participate in the immune response against parasites and viruses.

The signal transduction of CCR4 exhibits rapid desensitization characteristics. After binding with ligands, it is quickly internalized. This mechanism not only ensures the timeliness of chemotactic responses but also prevents excessive inflammatory damage.

Applications of CCR4 and CCR4 Antibody in Literature

1. Yoshie, Osamu. "CCR4 as a therapeutic target for cancer immunotherapy." Cancers 13.21 (2021): 5542. https://doi.org/10.3390/cancers13215542

The article indicates that CCR4 is a receptor expressed in T cells such as Th2 and Treg, as well as in T-cell malignancies like ATLL and CTCL. Moglializumab, as a humanized monoclonal antibody targeting CCR4, can effectively eliminate malignant T cells and Tregs, showing potential in the treatment of T-cell lymphoma and solid tumors, but it may cause adverse skin reactions and graft-versus-host disease.

2. Chalabi Hagkarim, Nafiseh, and Roger J. Grand. "The regulatory properties of the Ccr4–Not complex." Cells 9.11 (2020): 2379. https://doi.org/10.3390/cells9112379

The article indicates that Ccr4-Not is a structurally conserved multifunctional complex that coordinates gene expression in the nucleus and cytoplasm in both yeast and mammals by regulating mechanisms such as transcription and mRNA degradation.

3. Bogacka, Joanna, et al. "CC chemokine receptor 4 (CCR4) as a possible new target for therapy." International Journal of Molecular Sciences 23.24 (2022): 15638. https://doi.org/10.3390/ijms232415638

The article indicates that CCR4 is a chemokine receptor, and its ligands are involved in various diseases such as immunity, tumors, and neuropathic pain. Its pharmacological blocking not only treats immune inflammation but also has analgesic effects, making it a potential new therapeutic target.

4. Khabipov, Aydar, et al. "CCR4 blockade diminishes intratumoral macrophage recruitment and augments survival of syngeneic pancreatic cancer-bearing mice." Biomedicines 11.6 (2023): 1517. https://doi.org/10.3390/biomedicines11061517

The article indicates that CCR4 plays a key role in regulating the infiltration of tumor-associated macrophages (Tams) and tumor progression in pancreatic cancer. Studies have confirmed that blocking CCR4 through gene knockout or antagonists can effectively reduce TAM recruitment, inhibit tumor growth and prolong the survival period of mice, suggesting its potential as a new target for pancreatic cancer treatment.

5. Deng, Shuixiang, et al. "Recombinant CCL17-dependent CCR4 activation alleviates neuroinflammation and neuronal apoptosis through the PI3K/AKT/Foxo1 signaling pathway after ICH in mice." Journal of Neuroinflammation 18.1 (2021): 62. https://doi.org/10.1186/s12974-021-02112-3

This study confirmed that activating the CCR4 receptor after cerebral hemorrhage can alleviate neuroinflammation and neuronal apoptosis through the PI3K/AKT/Foxo1 signaling pathway, improve cerebral edema and neurological deficits, and provide a new strategy for the early treatment of cerebral hemorrhage.

Creative Biolabs: CCR4 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CCR4 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom CCR4 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CCR4 antibodies, custom preparations, or technical support, contact us at email.

Reference

Bogacka, Joanna, et al. "CC chemokine receptor 4 (CCR4) as a possible new target for therapy." International Journal of Molecular Sciences 23.24 (2022): 15638. https://doi.org/10.3390/ijms232415638