Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 195, Issue 12, Pages 1586-1596Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201609-1846OC
Keywords
ILC2; Th2; allergic airway inflammation; asthma
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Funding
- St. Mary's Flow Cytometry Core Facility, National Heart and Lung Institute, Imperial College London
- Asthma UK [MRC-AsthmaUKCentre, CH11SJ, MRC-Asthma UK Centre] Funding Source: researchfish
- Medical Research Council [G1000758, G1100238] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10092, CL-2016-21-007] Funding Source: researchfish
- MRC [G1100238] Funding Source: UKRI
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Rationale: 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. Objectives: To assess the role of ILC2s during nasal allergen challenge in subjects with allergic rhinitis using novel noninvasive methodology. Methods: 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. Measurements and Main Results: 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. Conclusions: 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 aexoallergens in the airways. The novel methodology described herein enables the analysis of rare cell populations from noninvasive serial tissue sampling.
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