Francis J N, Sabroe I, Lloyd C M, Durham S R, Till S J
Section of Allergy and Clinical Immunology, Imperial College London, London, UK.
Clin Exp Immunol. 2008 Jun;152(3):440-7. doi: 10.1111/j.1365-2249.2008.03657.x. Epub 2008 Apr 16.
CCR6 is expressed by multiple leucocyte subsets, including peripheral blood memory T cells, and mouse models implicate a role for this receptor in diverse inflammatory responses that include allergic airway disorders, inflammatory bowel disease and autoimmune encephalitis. In order to study the role of CCR6 in humans, we have investigated the patterns of CCR6 expression and function on T cells from the peripheral blood, skin, nose and lung, in health and in allergic disease. Results show that CCR6 was expressed consistently on a higher proportion of tissue versus peripheral blood-derived CD4+ T cells (P < 0.01). CCR6 was expressed predominantly on CD4+ compared with CD8+ cells in both blood- and tissue-derived T cells (P < 0.001). The number of cells showing CCR6 expression was not proportionally greater in peripheral blood or nasal mucosal T cells of subjects with symptomatic allergic rhinitis. CCR6+ cells demonstrated enhanced functional responses to CCL20 and CCL20 was increased in bronchoalveolar lavage fluid of asthmatics following endobronchial allergen provocation (P < 0.05). Thus, CCR6 may be important in the regulation of T cell recruitment to tissue and up-regulation of CCL20 expression may contribute to the recruitment and/or retention of effector T cells in allergic asthma.
CCR6由多种白细胞亚群表达,包括外周血记忆T细胞,小鼠模型表明该受体在多种炎症反应中起作用,这些炎症反应包括过敏性气道疾病、炎症性肠病和自身免疫性脑炎。为了研究CCR6在人类中的作用,我们调查了健康和过敏性疾病状态下,外周血、皮肤、鼻子和肺中T细胞上CCR6的表达模式和功能。结果显示,与外周血来源的CD4+ T细胞相比,组织来源的CD4+ T细胞中CCR6的表达比例始终更高(P < 0.01)。在血液和组织来源的T细胞中,与CD8+细胞相比,CCR6主要在CD4+细胞上表达(P < 0.001)。有症状的过敏性鼻炎患者外周血或鼻黏膜T细胞中,显示CCR6表达的细胞数量并没有相应增加。CCR6+细胞对CCL20表现出增强的功能反应,并且在支气管内过敏原激发后,哮喘患者的支气管肺泡灌洗液中CCL20增加(P < 0.05)。因此,CCR6可能在调节T细胞向组织的募集方面很重要,CCL20表达的上调可能有助于过敏性哮喘中效应T细胞的募集和/或滞留。