CCR4 blockade does not inhibit allergic airways inflammation

Journal of Leukocyte Biology

Dolores M. Conroy²  Ian Sabroe²  Martin R. Hodge¹  Timothy J. Williams²  Louise A. Jopling²  Clare M. Lloyd²  David P. Andrew¹  James E. Pease² 

[1] Millennium Pharmaceuticals Inc., Cambridge Massachusetts Millennium Pharmaceuticals Inc., Cambridge Massachusetts Millennium Pharmaceuticals Inc., Cambridge Massachusetts;Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, United Kingdom; and Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, United Kingdom; and Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, United Kingdom; and

关键词: T lymphocytes;    chemokines;    allergy;   

DOI  :  10.1189/jlb.0103030

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown