Farrell E, O'Connor T M, Duong M, Watson R M, Strinich T, Gauvreau G M, O'Byrne P M
Department of Medicine, McMaster University, Hamilton, ON, Canada.
Allergy. 2007 Oct;62(10):1139-45. doi: 10.1111/j.1398-9995.2007.01465.x.
Dendritic cells are key contributors to initiation and maintenance of T-cell immunity to inhaled allergen. The purpose of this study was to enumerate the changes in peripheral blood myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), the DCs expressing chemokine receptor 6 (CCR6) and chemokine receptor 7 (CCR7), following diluent and allergen inhalation in asthmatic subjects.
Peripheral blood was obtained from 16 allergic asthmatic subjects before and at 0.5, 1, 2, 3, 4, 6, 24, and 48 h after inhaled diluent and allergen challenges. Dendritic cells were enumerated using flow cytometry.
Allergen inhalation significantly reduced mDCs at 6 h (21.3 +/- 2.0 vs 15.0 +/- 1.8/microl blood; P < 0.05) and 24 h (21.5 +/- 3.4 vs 16.4 +/- 2.4/microl blood; P < 0.05) after challenge. Circulating pDCs were significantly lower than baseline up to 24 h after both allergen and diluent challenges. There was a significant efflux of CCR6(+) mDCs from peripheral blood at 6 h and CCR6(+) pDCs at 4 h after allergen challenge, when compared with diluent. There was no difference in the number of circulating CCR7(+) mDCs or pDCs after diluent or allergen challenges.
Peripheral blood mDCs and CCR6(+) mDCs, but not pDCs, are reduced up to 24 h after allergen inhalation. Thus, allergen inhalation causes trafficking of immature CCR6(+) DCs from blood into the airway, while that of the trafficking of the mature CCR7(+) DCs from the airways into the regional lymph nodes probably occurs through the lymphatic system.
树突状细胞是启动和维持针对吸入性变应原的T细胞免疫的关键因素。本研究的目的是列举哮喘患者吸入稀释剂和变应原后外周血髓样树突状细胞(mDCs)和浆细胞样树突状细胞(pDCs)、表达趋化因子受体6(CCR6)和趋化因子受体7(CCR7)的树突状细胞的变化。
从16名过敏性哮喘患者在吸入稀释剂和变应原激发前以及激发后0.5、1、2、3、4、6、24和48小时采集外周血。使用流式细胞术对树突状细胞进行计数。
变应原吸入在激发后6小时(21.3±2.0对15.0±1.8/微升血液;P<0.05)和24小时(21.5±3.4对16.4±2.4/微升血液;P<0.05)显著降低mDCs。在变应原和稀释剂激发后长达24小时,循环pDCs显著低于基线水平。与稀释剂相比,变应原激发后6小时外周血中CCR6(+) mDCs和4小时CCR6(+) pDCs有显著外流。稀释剂或变应原激发后循环CCR7(+) mDCs或pDCs的数量没有差异。
变应原吸入后长达24小时外周血mDCs和CCR6(+) mDCs减少,但pDCs未减少。因此,变应原吸入导致未成熟的CCR6(+) DCs从血液转运至气道,而成熟的CCR7(+) DCs从气道转运至区域淋巴结可能是通过淋巴系统发生的。