CCR4 blockade does not inhibit allergic airways inflammation.
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.
Conroy
Dolores M
DM
Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College, London, United Kingdom.
Jopling
Louise A
LA
Lloyd
Clare M
CM
Hodge
Martin R
MR
Andrew
David P
DP
Williams
Timothy J
TJ
Pease
James E
JE
Sabroe
Ian
I
D000818:Animals; D001249:Asthma / Q000209:etiology / Q000628:therapy*; D002465:Cell Movement; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000096:biosynthesis; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D054422:Chemokine CCL22; D019742:Chemokines, CC; D054398:Receptors, CCR4; D019707:Receptors, Chemokine