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CCR4 blockade does not inhibit allergic airways inflammation
Author(s) -
Conroy Dolores M.,
Jopling Louise A.,
Lloyd Clare M.,
Hodge Martin R.,
Andrew David P.,
Williams Timothy J.,
Pease James E.,
Sabroe Ian
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0103030
Subject(s) - ccr4 , immunology , eotaxin , cc chemokine receptors , chemokine , ccl22 , chemokine receptor , bronchoalveolar lavage , allergic inflammation , inflammation , biology , medicine , lung
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.