Yamashita Naomi, Tashimo Hiroyuki, Matsuo Yukiko, Ishida Hirofumi, Yoshiura Kenta, Sato Katsuaki, Yamashita Naohide, Kakiuchi Terutaka, Ohta Ken
Department of Pharmacology, Research Institute of Pharmaceutical Sciences, Musashino University, Shinmachi Nishitokyo-shi, Tokyo.
J Allergy Clin Immunol. 2006 May;117(5):1040-6. doi: 10.1016/j.jaci.2006.01.009.
Dendritic cells are the most powerful of the antigen-presenting cells and are known to play important roles in sensitization and inflammation in allergen-specific asthma. Various cytokines and chemokines are involved in the maturation and activation of dendritic cells. Among them is CC chemokine ligand (CCL)21, a key chemokine in the entry of naive T cells and antigen-stimulated dendritic cells into the T-cell zones of secondary lymphoid organs, which is a critical process in antigen-specific T-cell activation.
We studied the role of CCL21 in airway inflammation in asthma by using BALB/c-plt/plt (plt) mice, which possess genetic defects in expression of both CCL21 and CCL19.
Plt and control BALB/c mice were immunized with ovalbumin and alum 4 times and thereafter were subjected to a 2-week regimen of ovalbumin inhalation.
In plt mice, ovalbumin-specific IgE response was delayed compared with control BALB/c mice, but they had the same level of response after final immunization. Although airway inflammation and response to acetylcholine were significantly reduced compared with BALB/c mice, significant eosinophilic inflammation and hyperresponsiveness were also observed in plt mice after 2 weeks of inhalation. Four weeks after cessation of inhalation, airway inflammation and hyperresponsiveness in plt mice were greater than in BALB/c mice. At the time of resolution of airway inflammation, IL-10 production was enhanced in BALB/c mice but not in plt mice.
The chemokines CCL21 and CCL19 were critical for resolution of airway inflammation.
The findings about the chemokines for induction and resolution of inflammation are key to establishing a new strategy for asthma immunotherapy.
树突状细胞是最强大的抗原呈递细胞，已知其在变应原特异性哮喘的致敏和炎症中发挥重要作用。多种细胞因子和趋化因子参与树突状细胞的成熟和激活。其中CC趋化因子配体（CCL）21是未成熟T细胞和抗原刺激的树突状细胞进入二级淋巴器官T细胞区的关键趋化因子，这是抗原特异性T细胞激活中的一个关键过程。
我们通过使用在CCL21和CCL19表达上存在基因缺陷的BALB/c-plt/plt（plt）小鼠，研究CCL21在哮喘气道炎症中的作用。
用卵清蛋白和明矾对plt小鼠和对照BALB/c小鼠进行4次免疫，之后进行为期2周的卵清蛋白吸入方案。
与对照BALB/c小鼠相比，plt小鼠的卵清蛋白特异性IgE反应延迟，但在最后一次免疫后它们具有相同的反应水平。虽然与BALB/c小鼠相比气道炎症和对乙酰胆碱的反应显著降低，但在吸入2周后plt小鼠中也观察到明显的嗜酸性粒细胞炎症和高反应性。停止吸入4周后，plt小鼠的气道炎症和高反应性大于BALB/c小鼠。在气道炎症消退时，BALB/c小鼠中IL-10的产生增强，而plt小鼠中则未增强。
趋化因子CCL21和CCL19对气道炎症的消退至关重要。
关于炎症诱导和消退的趋化因子的研究结果是建立哮喘免疫治疗新策略的关键。
