CCR4 blockade does not inhibit allergic airways inflammation. 2003

Dolores M Conroy, and Louise A Jopling, and Clare M Lloyd, and Martin R Hodge, and David P Andrew, and Timothy J Williams, and James E Pease, and Ian Sabroe
Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College, London, United Kingdom.

The CC chemokine receptor 4 (CCR4) shows selectivity for the recruitment of memory T cell subsets, including those of the T helper cell type 2 (Th2) phenotype. In humans, CCR4+ T cells are recruited to the asthmatic lung in response to allergen challenge; however, the contribution of this pathway to allergic disease remains uncertain. We therefore investigated the role of CCR4 in allergic airways inflammation in the guinea pig. Blockade of CCR4 with a specific antibody resulted in only minor changes in numbers of CCR4+ Th cells in the bronchoalveolar lavage fluid of allergen-challenged guinea pigs and failed to inhibit the generation of eotaxin/CC chemokine ligand (CCL)11 or macrophage-derived chemokine/CCL22 or the recruitment of inflammatory leukocytes to the lung. These data suggest that although CCR4 was originally proposed as a marker of Th2 status, antigen-specific Th2 cells are recruited to the lung predominantly by other pathways. This study casts doubts on the validity of CCR4 as a therapeutic target in the treatment of asthma.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D054398 Receptors, CCR4 CCR receptors with specificity for CHEMOKINE CCL17 and CHEMOKINE CCL22. They are expressed at high levels in T-LYMPHOCYTES; MAST CELLS; DENDRITIC CELLS; and NK CELLS. Antigens, CD194,CC Chemokine Receptor 4,CCR4 Receptors,CD194 Antigens,CC Chemokine Receptors 4,CCR4 Receptor,CD194 Antigen,Antigen, CD194,Receptor, CCR4
D054422 Chemokine CCL22 A CC-type chemokine with specificity for CCR4 RECEPTORS. It has activity towards TH2 CELLS and TC2 CELLS. CCL22 Chemokine,CC Chemokine STCP-1,Macrophage-Derived Chemokine,SCYA22 Chemokine,Small Inducible Cytokine A22,Stimulated T Cell Chemotactic Protein 1,CC Chemokine STCP 1,CCL22, Chemokine,Chemokine STCP-1, CC,Chemokine, CCL22,Chemokine, Macrophage-Derived,Chemokine, SCYA22,Macrophage Derived Chemokine,STCP-1, CC Chemokine
D018418 Th2 Cells A subset of helper-inducer T-lymphocytes which synthesize and secrete the INTERLEUKINS IL-4; IL-5; IL-6; and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses. T Helper 2 Cell,T Helper2 Cell,TH-2 Cell,Th2 Cell,Type-2 Helper T Cell,T Helper 2 Cells,T Helper2 Cells,TH-2 Cells,Type-2 Helper T Cells,Cell, T Helper2,Cell, TH-2,Cell, Th2,Cells, T Helper2,Cells, TH-2,Cells, Th2,TH 2 Cell,TH 2 Cells,Type 2 Helper T Cell,Type 2 Helper T Cells
D019707 Receptors, Chemokine Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif. Chemokine Receptor,Chemokine Receptors,Receptor, Chemokine

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