de Nadaï Patricia, Charbonnier Anne-Sophie, Chenivesse Cécile, Sénéchal Stéphanie, Fournier Clément, Gilet Jules, Vorng Han, Chang Ying, Gosset Philippe, Wallaert Benoît, Tonnel André-Bernard, Lassalle Philippe, Tsicopoulos Anne
Institut National de la Sante et de la Recherche Medicale U-774, Institut Pasteur de Lille, 59019 Lille Cedex, France.
J Immunol. 2006 May 15;176(10):6286-93. doi: 10.4049/jimmunol.176.10.6286.
Allergic asthma is associated with a pulmonary recruitment of Th type 2 cells, basophils, and eosinophils, mainly linked to chemokine production. CCL18 is a chemokine preferentially expressed in the lung, secreted by APCs, induced by Th2-type cytokines, and only present in humans. Therefore, CCL18 may be involved in allergic asthma. PBMC from asthmatics allergic to house dust mite cultured in the presence of Dermatophagoides pteronyssinus 1 (Der p 1) allergen secreted CCL18, 48 and 72 h after stimulation, whereas those from healthy donors did not. Part of CCL18 was directly derived from Der p 1-stimulated plasmacytoid dendritic cells, whereas the other part was linked to monocyte activation by IL-4 and IL-13 produced by Der p 1-stimulated T cells. In bronchoalveolar lavages from untreated asthmatic allergic patients, CCL18 was highly increased compared with controls. Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release. These data show a new function for CCL18, i.e., the recruitment of Th2 cells and basophils, and suggest that CCL18 may play a predominant role in allergic asthma.
过敏性哮喘与肺部募集2型辅助性T细胞、嗜碱性粒细胞和嗜酸性粒细胞有关，这主要与趋化因子的产生有关。CCL18是一种优先在肺部表达的趋化因子，由抗原呈递细胞分泌，由2型辅助性T细胞因子诱导，且仅在人类中存在。因此，CCL18可能参与过敏性哮喘。在粉尘螨1（Der p 1）变应原存在的情况下培养的对屋尘螨过敏的哮喘患者的外周血单核细胞（PBMC），在刺激后48小时和72小时分泌CCL18，而健康供体的PBMC则不分泌。部分CCL18直接来源于Der p 1刺激的浆细胞样树突状细胞，而另一部分则与Der p 1刺激的T细胞产生的白细胞介素-4和白细胞介素-13激活单核细胞有关。在未经治疗的过敏性哮喘患者的支气管肺泡灌洗液中，与对照组相比，CCL18显著增加。在功能上，CCL18优先吸引体外极化的2型辅助性T细胞和嗜碱性粒细胞，但不吸引嗜酸性粒细胞和1型辅助性T细胞，并诱导嗜碱性粒细胞组胺释放和细胞内钙释放。这些数据显示了CCL18的一种新功能，即募集2型辅助性T细胞和嗜碱性粒细胞，并表明CCL18可能在过敏性哮喘中起主要作用。
