Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation
Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation
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DOI：
10.4049/jimmunol.178.1.480
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
--
作者：
Kitamura, Kenichi;Takeda, Katsuyuki;Gelfand, Erwin W.
FER公共Y链(FcRy)是多种炎性细胞上表达的受体Fe epsilon RI、Fc Gamma RI和Fc Gamma RIII的重要组成部分。这些受体在启动或维持变态反应性炎症中的作用尚未很好地确定。FCRγ缺陷型(FcRy(-/-))和对照(野生型(WT))分别致敏小鼠，然后用卵清蛋白攻击。在对OVA致敏和攻击后，Fery缺陷(FcRy(-/-))小鼠的IgE和IgG1水平与WT小鼠相当。然而，嗜酸性粒细胞数量、支气管肺泡灌洗液中IL-5、IL-13和嗜酸性粒细胞趋化因子水平以及单核细胞(MNC)对OVA的增殖反应显著降低，吸入乙酰甲胆碱的气道高反应性(AHR)也显著降低。用WT小鼠致敏前的全脾MNC重建Fery(-/-)小鼠，可恢复AHR的发育和支气管肺泡灌洗液中嗜酸粒细胞的数量，致敏后OVA激发前的重建只能部分恢复上述反应。当FcRy(-/-)小鼠在致敏FCR(+/+)或Fe-Gamma RIII缺陷小鼠而不是FcRy(-/-)小鼠致敏之前接受T细胞耗尽的MNC、T和B细胞耗尽的MNC或骨髓来源的树突状细胞时，这些反应也得到恢复。FCR(+/+)小鼠骨髓来源的树突状细胞上Fc-γrv的表达水平较低。这些结果表明，在过敏性呼吸道炎症和AHR的致敏阶段，APC上FCR-γ的表达，很可能是Fc-Gamma RI的表达是重要的。
The FeR common y-chain (FcRy) is an essential component of the receptors Fe epsilon RI, Fc gamma RI, and Fc gamma RIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcR gamma-deficient (FcRy(-/-)) and control (wild-type (WT)), mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FeRy-deficient (FcRy(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FeRy(-/-) mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRy(-/-) mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR(+/+) or Fe gamma RIII-deficient but not FcRy(-/-) mice. The expression levels of Fc gamma RIV on bone marrow-derived dendritic cells from FcR(+/+) mice were found to be low. These results demonstrate that expression of FcR gamma, most likely Fc gamma RI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.