Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, London, UK.
Allergy. 2010 Sep;65(9):1126-33. doi: 10.1111/j.1398-9995.2010.02327.x. Epub 2010 Feb 10.
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.
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-gamma 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.
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-gamma. CCR4(+)CD4(+) T cells responded to MDC in vitro, and this response was inhibited by the selective CCR4 antagonist.
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.
CC 趋化因子受体 4（CCR4）优先表达于 Th2 淋巴细胞。CCR4 介导的炎症可能在变应性鼻炎的病理过程中发挥重要作用。破坏 CCR4-配体相互作用可能会阻断变应原诱导的炎症。
16 名变应性鼻炎患者和 6 名非变应性个体均接受变应原和对照（稀释剂）鼻内激发。记录症状评分和最大鼻吸气峰流速。在激发后 8 小时采集鼻活检标本。免疫组织化学染色，用光镜或双免疫荧光显微镜观察嗜酸性粒细胞、T 淋巴细胞、CCR4+CD3+和 CXCR3+CD3+细胞，原位杂交检测 CCR4、IL-4 和 IFN-γ mRNA+细胞。从 9 名正常供者外周血中获取外周血单个核细胞，评估 CCR4 配体巨噬细胞来源趋化因子（MDC/CCL22）诱导的 CCR4+CD4+细胞肌动蛋白聚合反应，以及测试 CCR4 拮抗剂的影响。
与稀释剂相比，变应性鼻炎患者在变应原激发后出现早发和迟发相症状增加；而非变应性个体对两种激发均无反应。变应性鼻炎患者在变应原激发后，嗜酸性粒细胞而非总 CD3+T 细胞数量增加。与 CXCR3+CD3+细胞相比，变应性鼻炎患者 CCR4+CD3+蛋白阳性细胞增加；CCR4 mRNA+细胞增加，IL-4 增加的程度大于 IFN-γ。体外 CCR4+CD4+T 细胞对 MDC 有反应，这种反应可被选择性 CCR4 拮抗剂抑制。
淋巴细胞 CCR4 表达与诱导人类变应原诱导的迟发性鼻反应密切相关。阻断 CCR4-配体相互作用可能为变应性疾病提供一种新的治疗方法。
