Rapid recruitment of CD14+ monocytes in experimentally induced allergic rhinitis in human subjects

CD14型 免疫学 趋化因子 促炎细胞因子 炎症 人口 外周血单个核细胞 四氯化碳 单核细胞 过敏性炎症 医学 吞噬细胞 生物 免疫系统 体外 环境卫生 生物化学
作者
Ibon Eguíluz‐Gracia,Anthony Bosco,Ralph Dollner,Guro Reinholt Melum,Maria H. Lexberg,Anya C. Jones,Sinan Dheyauldeen,Patrick G. Holt,Espen S. Bækkevold,Frode L. Jahnsen
出处
期刊:The Journal of Allergy and Clinical Immunology [Elsevier]
卷期号:137 (6): 1872-1881.e12 被引量:54
标识
DOI:10.1016/j.jaci.2015.11.025
摘要

Activated TH2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract T cells and eosinophils to the inflammatory lesion has not been determined.We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction.Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling.In an in vivo model of AR, we found that CD14(+) monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1 week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several TH2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4(+) T cells and eosinophils.Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14(+) monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation.
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