CCR4 blockade does not inhibit allergic airways inflammation
Open Access
- 15 July 2003
- journal article
- extracellular mediators-and-effector-molecules
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 74 (4) , 558-563
- https://doi.org/10.1189/jlb.0103030
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
Funding Information
- National Asthma Campaign
- Wellcome Trust (038775/Z/96/A)
- Imperial College of Science, Technology and Medicine
- Millennium Pharmaceuticals Inc.
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