Coordinated involvement of mast cells and T cells in allergic mucosal inflammation:: Critical role of the CC chemokine ligand 1:CCR8 axis
Coordinated involvement of mast cells and T cells in allergic mucosal inflammation:: Critical role of the CC chemokine ligand 1:CCR8 axis
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DOI：
10.4049/jimmunol.179.3.1740
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Coyle, Anthony J.
中科院分区：
文献类型：
--
作者：
Gonzalo, Jose-Angel;Qiu, Yubin;Coyle, Anthony J.
CCL 1是体外由IgE激活的人和小鼠肥大细胞分泌的主要趋化因子，在肺活检中共定位于肥大细胞，并且在哮喘气道中升高。CCL 1的受体CCR 8在哮喘气道募集的CD 4（+）T淋巴细胞中的表达率接近70%，与正常志愿者相比，哮喘受试者气道中表达CCR 8的细胞数量增加了3倍。在体内，在吸入过敏原激发后，肥大细胞缺陷小鼠肺中的CCL 1表达减少。CCL 1或CCR 8缺陷的中和导致肺粘膜炎症、气道高反应性和粘液分泌过多减少，其程度与肥大细胞缺陷小鼠中检测到的相似。腺病毒将CCL 1递送至肥大细胞缺陷小鼠的肺部，可将气道高反应性、肺部炎症和粘液分泌过多恢复到野生型小鼠中观察到的程度。CCR 8缺陷的后果，包括Th 2细胞因子水平的显著降低，与CD 4（+）T淋巴细胞耗竭所观察到的结果相当。因此，肥大细胞衍生的CCL 1-和表达CD 4（+）的效应T淋巴细胞在协调肺粘膜炎症反应中发挥重要作用。
CCL1 is the predominant chemokine secreted from IgE-activated human and mouse mast cells in vitro, colocalizes to mast cells in lung biopsies, and is elevated in asthmatic airways. CCR8, the receptor for CCL1, is expressed by similar to 70% of CD4(+) T lymphocytes recruited to the asthmatic airways, and the number of CCR8-expressing cells is increased 3-fold in the airways of asthmatic subjects compared with normal volunteers. In vivo, CCL1 expression in the lung is reduced in mast cell-deficient mice after aeroallergen provocation. Neutralization of CCL1 or CCR8 deficiency results in reduced mucosal lung inflammation, airway hyperresponsiveness, and mucus hypersecretion to a similar degree as detected in mast cell-deficient mice. Adenoviral delivery of CCL1 to the lungs of mast cell-deficient mice restores airway hyperresponsiveness, lung inflammation, and mucus hypersecretion to the degree observed in wild-type mice. The consequences of CCR8 deficiency, including a marked reduction in Th2 cytokine levels, are comparable with those observed by depletion of CD4(+) T lymphocytes. Thus, mast cell-derived CCL1 - and expressing CD4(+) effector T lymphocytes play an essential role in orchestrating lung mucosal inflammatory responses.