Dhariwal Jaideep, Cameron Aoife, Trujillo-Torralbo Maria-Belen, Del Rosario Ajerico, Bakhsoliani Eteri, Paulsen Malte, Jackson David J, Edwards Michael R, Rana Batika M J, Cousins David J, Hansel Trevor T, Johnston Sebastian L, Walton Ross P
1 Airway Disease Infection Section, National Heart and Lung Institute, London, United Kingdom.
2 Medical Research Council Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
Am J Respir Crit Care Med. 2017 Jun 15;195(12):1586-1596. doi: 10.1164/rccm.201609-1846OC.
Newly characterized type 2 innate lymphoid cells (ILC2s) display potent type 2 effector functionality; however, their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterize the airway mucosa is invasive, poorly tolerated, and does not allow for sequential sampling.
To assess the role of ILC2s during nasal allergen challenge in subjects with allergic rhinitis using novel noninvasive methodology.
We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of ILC2s and granulocytes to the upper airways of subjects with atopy and healthy subjects after allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption.
After an allergen challenge, subjects with atopy displayed rapid induction of upper airway symptoms, an enrichment of ILC2s, eosinophils, and neutrophils, along with increased production of IL-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared with healthy subjects. The most pronounced ILC2 recruitment was observed in subjects with elevated serum IgE and airway eosinophilia.
The rapid recruitment of ILC2s to the upper airways of allergic patients with rhinitis, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.
新鉴定出的2型固有淋巴细胞(ILC2s)具有强大的2型效应功能;然而,它们在过敏性气道炎症和哮喘中的作用尚不清楚。用于表征气道黏膜的黏膜活检具有侵入性,耐受性差,且不允许进行连续采样。
使用新型非侵入性方法评估ILC2s在变应性鼻炎患者鼻腔过敏原激发过程中的作用。
我们使用人类实验性过敏原激发模型,通过对鼻腔刮除样本进行流式细胞术分析,评估特应性受试者和健康受试者在过敏原激发后ILC2s和粒细胞向上呼吸道的募集情况。使用鼻吸附法测量鼻黏膜衬液中的可溶性介质。
过敏原激发后,与健康受试者相比,特应性受试者出现上呼吸道症状的快速诱导、ILC2s、嗜酸性粒细胞和中性粒细胞的富集,以及IL-5、前列腺素D2、嗜酸性粒细胞和2型辅助性T细胞趋化因子的产生增加。在血清IgE升高和气道嗜酸性粒细胞增多的受试者中观察到最明显的ILC2募集。
ILC2s快速募集到变应性鼻炎患者的上呼吸道,且它们与关键的2型介质相关,这突出了它们在气道对气传过敏原的早期过敏反应中可能发挥的重要作用。本文所述的新型方法能够对来自非侵入性连续组织采样的稀有细胞群体进行分析。