CC Chemokine Receptor 4 (CCR4) in human allergen‐induced late nasal responses

Abstract

To cite this article: Banfield G, Watanabe H, Scadding G, Jacobson MR, Till SJ, Hall DA, Robinson DS, Lloyd CM, Nouri‐Aria KT, Durham SR. CC Chemokine Receptor 4 (CCR4) in human allergen‐induced late nasal responses. Allergy 2010; 65: 1126–1133. Abstract Background: CC Chemokine receptor 4 (CCR4) is preferentially expressed on Th2 lymphocytes. CCR4‐mediated inflammation may be important in the pathology of allergic rhinitis. Disruption of CCR4 – ligand interaction may abrogate allergen‐induced inflammation. Methods: Sixteen allergic rhinitics and six nonatopic individuals underwent both allergen and control (diluent) nasal challenges. Symptom scores and peak nasal inspiratory flow were recorded. Nasal biopsies were taken at 8 h post challenge. Sections were immunostained and examined by light or dual immunofluorescence microscopy for eosinophils, T‐lymphocytes, CCR4⁺CD3⁺ and CXCR3⁺CD3⁺ cells and examined by in situ hybridization for CCR4, IL‐4 and IFN‐γ mRNA⁺ cells. Peripheral blood mononuclear cells were obtained from peripheral blood of nine normal donors and the CCR4⁺CD4⁺ cells assessed for actin polymerization in response to the CCR4 ligand macrophage‐derived chemokine (MDC/CCL22) and the influence of a CCR4 antagonist tested. Results: Allergic rhinitics had increased early and late phase symptoms after allergen challenge compared to diluent; nonatopics did not respond to either challenge. Eosinophils, but not total numbers of CD3⁺ T cells, were increased in rhinitics following allergen challenge. In rhinitics, there was an increase in CCR4⁺CD3⁺ protein‐positive cells relative to CXCR3⁺CD3⁺ cells; CCR4 mRNA+ cells were increased and IL‐4 increased to a greater extent than IFN‐γ. CCR4⁺CD4⁺ T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist. Conclusion: Lymphocyte CCR4 expression is closely associated with induction of human allergen‐induced late nasal responses. Blocking CCR4‐ligand interaction may provide a novel therapeutic approach in allergic disease.