Department of Medicine, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America.
PLoS One. 2019 Sep 6;14(9):e0217807. doi: 10.1371/journal.pone.0217807. eCollection 2019.
Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our results demonstrate that IL-33 can produce as potent eosinophil activation as IL-3, IL-5 and eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to consider for modulating eosinophil function.
嗜酸性粒细胞是参与过敏性哮喘、特应性皮炎、嗜酸性食管炎和高嗜酸性粒细胞综合征的主要炎症细胞,在受影响患者的局部组织和/或循环血液中数量较多。最近人们对一组警报素(包括 TSLP、IL-25 和 IL-33)产生了兴趣,这些警报素是上皮细胞衍生的,并在上皮细胞受到刺激时释放。几项全基因组关联研究发现,编码 IL-33 的基因中的 SNPs 是哮喘的风险因素。在两项研究中,检查了 IL-33 对嗜酸性粒细胞的直接作用,发现嗜酸性粒细胞的反应存在差异。我们试图进一步描述与其他细胞因子和趋化因子相比,IL-33 对嗜酸性粒细胞的激活作用。我们评估了 IL-33 刺激的黏附、脱颗粒、趋化和细胞表面蛋白表达,与 IL-3、IL-5 和 eotaxin-1 在人嗜酸性粒细胞上的作用进行了比较。我们的结果表明,IL-33 可以产生与 IL-3、IL-5 和 eotaxin-1 一样强烈的嗜酸性粒细胞激活作用。因此,在考虑特定细胞因子靶向策略时,IL-33 将是调节嗜酸性粒细胞功能的重要因素。