Expression of CCR8 is increased in asthma

BACKGROUND: Chemokines and their receptors could play key roles in the recruitment of T cells to the asthmatic lung. CCR8 is preferentially expressed on T-helper type 2 cells, and is thought to play a role in the pathogenesis of human asthma. OBJECTIVE: Determine the expression of CCR8 on T cells in blood, bronchoalveolar lavage (BAL) and bronchial mucosa from asthmatics and normal subjects. METHODS: CCR8 expression in blood and BAL from asthma and normal subjects was studied using flow cytometry. CCR8 expression on IFN-γ(+) and IL-4(+)/IL-13(+) blood and BAL T cells was studied following stimulation with Phorbol–Myristate–Acetate and Calcium Ionophore. Paraffin-embedded bronchial biopsies were used to study CCR8 in bronchial epithelium. RESULTS: The percentage of CD3(+) cells expressing CCR8 in the blood was higher in asthmatics (4.7±0.4%) compared with normal subjects (3.0±0.4%; P<0.01). There was an approximately sixfold enrichment of CCR8 on IL-4(+)/IL-13(+) cells compared with IFN-γ(+) T cells (P<0.001) in both asthmatic and normal subjects in both blood and BAL. Significantly more BAL T cells expressed CCR8 in asthmatic (8.6±0.8%) compared with normal subjects (3.9±0.7%) (P<0.01). In paired blood-BAL samples from asthmatics, significantly more CCR8+CD3(+) T cells were present in BAL (9.0±0.9%) than in blood (5.6±0.9%; P<0.05). There were more CCR8-positive cells in bronchial biopsies from asthmatic (93±11 cells/mm(2)) compared with normal subjects (30±16 cells/mm(2)) (P<0.05). The ligand CCL1 was increased in the BAL of asthmatics compared with normal subjects (35±6 vs. 12.9±7 pg/mL; P<0.05). CONCLUSION: There may be a role for CCR8 in the recruitment of T cells to the lung in asthmatics. Cite this as: K. Mutalithas, C. Guillen, C. Raport, R. Kolbeck, D. Soler, C. E. Brightling, I. D. Pavord and A. J. Wardlaw, Clinical & Experimental Allergy, 2010 (40) 1175–1185.