CD1d expressed in mast cell surface enhances IgE production in B cells by up-regulating CD40L expression and mediator release in allergic asthma in mice
CD1d expressed in mast cell surface enhances IgE production in B cells by up-regulating CD40L expression and mediator release in allergic asthma in mice
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DOI：
10.1016/j.cellsig.2014.01.029
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发表时间：
2014-05-01
影响因子：
4.8
通讯作者：
Ro, Jai Youl
中科院分区：
文献类型：
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作者：
Hong, Gwan Ui;Kim, Nam Goo;Ro, Jai Youl
肥大细胞通过 Fc epsilon RI 介导的激活在过敏性哮喘中发挥重要作用。非多态性 MHC I 样分子 CD1d 主要在 APC 中表达，将糖脂 Ag 呈递给 iNKT 细胞上的 iTCR 并调节过敏反应。本研究旨在探讨 CD1d 对过敏性哮喘相关 IgE 产生和肥大细胞激活的作用。在 iNKT 细胞存在的情况下，用 Ag/Ab（分别指 WT-act-BMMC 和 KO-act-BMMC）或 a-半乳糖神经酰胺（WT-α Gal-BMMC、KO-α Gal-BMMC）激活来自 C57BL/6 野生型 (WT) 或 KO (CD1d(-/-)) 小鼠的骨髓源性肥大细胞 (BMMC)。 WT、KO或BMM-C转移的KO小鼠被OVA或et-Gal致敏和/或攻击以诱导哮喘。与相应的 VVT-BMMC 相比，KO-act-BMMC 降低了细胞内 Ca2+ 水平、信号分子（Ras、Rac1/2、PLA(2)、COX-2、NF-kappa B/AP-1）的表达、介质释放（组胺、白三烯和细胞因子/趋化因子）以及总 IgE 水平。与相应的 WT 小鼠相比，KO 小鼠降低了总 IgE 水平和 OVA 特异性血清 IgE 水平、肥大细胞数量、募集分子（CCR2/CCL2、VCAM-1、PECAM-1）、类胰蛋白酶、c-kit、CD40L 和细胞因子 mRNA 的表达、BAL 细胞或肺组织中 c-kit 和 CD1d 或 iNKT 细胞的共定位以及 PCA 反应。与 KO-both 小鼠相比，BMMC 转移的 KO-both 小鼠表现出所有过敏反应的恢复（Ag/Ab 反应加 a-Gal）。 KO-aGal-BMMC 或 KO-α Gal 小鼠没有表现出任何反应。我们的数据表明，CD1d 表达的肥大细胞可能充当 iNKT 细胞的 APC 细胞，并通过 OVA 攻击小鼠肥大细胞中 B 细胞 Ig 类别转换和介质释放上调 IgE 产生，从而加剧气道炎症和重塑。 (C) 2014 年，爱思唯尔公司出版
Mast cells play important roles via Fc epsilon RI-mediated activation in allergic asthma. A nonpolymorphic MHC I-like molecule CD1d, which is mainly expressed in APCs, presents glycolipid Ag to iTCR on iNKT cells and modulates allergic responses. This study aimed to investigate the role of CD1d on IgE production and mast cell activation related to allergic asthma. Bone marrow-derived mast cells (BMMCs) from C57BL/6 Wild type (WT) or KO (CD1d(-/-)) mice were activated with Ag/Ab (refer to WT-act-BMMCs and KO-act-BMMCs, respectively) or a-Galactosylceramide (WT-alpha Gal-BMMCs, KO-alpha Gal-BMMCs) in the presence of iNKT cells. WT, KO or BMM-Ctransferred KO mice were sensitized and/or challenged by OVA or et-Gal to induce asthma. KO-act-BMMCs reduced intracellular Ca2+ levels, expression of signaling molecules (Ras, Rac1/2, PLA(2), COX-2, NF-kappa B/AP-1), mediator release (histamines, leukotrienes and cytokines/chemokines), and total IgE levels versus the corresponding VVT-BMMCs. KO mice reduced total and OVA-specific serum IgE levels, number of mast cells, recruiting molecules (CCR2/CCL2, VCAM-1, PECAM-1), expression of tryptase, c-kit, CD40L and cytokine mRNA, colocalization of c-kit and CD1d or iNKT cells in BAL cells or lung tissues, and PCA responses, compared with the corresponding WT mice. BMMC-transferred KO-both mice showed the restoration of all allergic responses versus KO-both mice (Ag/Ab reaction plus a-Gal). KO-aGal-BMMCs or KO-alpha Gal mice did not show any responses. Our data suggest that CD1d-expressed mast cells may function as APC cells for iNKT cells and exacerbate airway inflammation and remodeling through up-regulating IgE production via B cell Ig class switching and mediator release in mast cells of OVA-challenged mice. (C) 2014 Published by Elsevier Inc.