CCR4 blockade does not inhibit allergic airways inflammation

Dolores Conroy

Louise Jopling

Clare Lloyd

Martin Hodge

^{Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, United Kingdom}

^{Millennium Pharmaceuticals Inc., Cambridge Massachusetts}

^{Correspondence: Leukocyte Biology, Biomedical Sciences Division, Faculty of Medicine, Imperial College, South Kensington, London SW7 2AZ, UK.}ku.ca.lairepmi@eorbas.i

Abstract

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.}

Keywords: T lymphocytes, chemokines, allergy

Abstract

REFERENCES

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