CCL2/CCR2依赖的Th17细胞（非Tc17细胞）在哮喘小鼠模型的肺中的募集
2015/05/22
摘要
背景：白介素（IL）-17与哮喘的发病机制及气道炎症的进展相关。在此，我们通过小鼠过敏性哮喘模型发现，IL-17分泌型辅助T细胞（Th17）和CD8(Tc)17细胞的数量显著增加。这些细胞表面还同时表达CC趋化因子受体2（CCR2）。CC趋化因子配体2（CCL2）可介导哮喘患者体内炎症细胞的活化与募集，当加入卵清蛋白（OVA）后可被灭活。但是，CC趋化因子配体2对Th17细胞及Tc17细胞中的作用还未被阐明。
方法：经卵清蛋白致敏和激发的小鼠接受抗CCL2抗体（5 μg/天，气管内给药）或在卵清蛋白激发前给予CCR2拮抗剂（RS504393，2 mg/kg/天，腹腔内注射）。部分小鼠只采用同型对照抗体或通气治疗处理。评估过敏性哮喘和抗CCL2抗体或CCR2拮抗剂的治疗对IL-17和CCL2水平、Th17细胞和Tc17细胞数量以及肺组织炎症反应的影响。
结果：本研究结果显示，哮喘小鼠组较正常对照组小鼠肺组织以及支气管肺泡灌洗液中CCL2和IL-17水平高，且Th17和Tc17细胞数量增高。抑制CCL2/CCR2轴可显著降低Th17细胞的数量，但不能减少Tc17细胞的数量，揭示其对气道炎症具有一定抑制作用。
结论：本研究结果提示，在急性过敏性气道炎症中，CCL2/CCR2轴对调节Th17细胞而非Tc17细胞的迁移具有一定作用。
（杨冬 审校）
Int Arch Allergy Immunol. 2015 Mar 4;166(1):52-62. [Epub ahead of print]
CCL2/CCR2-Dependent Recruitment of Th17 Cells but Not Tc17 Cells to the Lung in a Murine Asthma Model.
Wang A1, Wang Z, Cao Y, Cheng S, Chen H, Bunjhoo H, Xie J, Wang C, Xu Y, Xiong W.
Author information
ABSTRACT
BACKGROUND:Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8 (Tc)17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells inasthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated.
METHODS:Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 μg/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an isotype control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation.
RESULTS:We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation.
CONCLUSION:These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation.
Int Arch Allergy Immunol. 2015 Mar 4;166(1):52-62. [Epub ahead of print]
