期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 204, 期 11, 页码 1259-1273出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.202010-3754OC
关键词
innate lymphoid cells; ILC1; ILC2; asthma; rhinovirus
资金
- Medical Research Council (MRC) [G1100238]
- GlaxoSmithKline Strategic Alliance Program grant [G1100238]
- National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme
- Asthma UK Centre grant [G1000758]
- Asthma UK Clinical Chair [CH11SJ]
- MRC [G1000758]
The study found that after experimental rhinovirus challenge, ILC2 levels were significantly higher in patients with asthma compared to healthy subjects, as well as the ILC2:ILC1 ratio. ILC2 may play an important role in virus-induced asthma exacerbations.
Rationale: Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well characterized. Objectives: To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects. Methods: Patients with moderate asthma and healthy subjects were inoculated with rhinovirus-16 and underwent bronchoscopy at baseline and at Day 3, and Day 8 after inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage using flow cytometry. The ratio of bronchoalveolar lavage ILC2:ILC1 was assessed to determine their relative contributions to the clinical and immune response to rhinovirus challenge. Measurements and Main Results: At baseline, ILC2s were significantly higher in patients with asthma than in healthy subjects. At Day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in patients with asthma than in healthy subjects (all comparisons P < 0.05). In healthy subjects, ILC1s increased from baseline at Day 3 (P = 0.001), while in patients with asthma, ILC1s increased from baseline at Day 8 (P = 0.042). Patients with asthma had significantly higher ILC2:ILC1 ratios at baseline (P = 0.024) and Day 8 (P = 0.005). Increased ILC2:ILC1 ratio in patients with asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid. Conclusions: An ILC2-predominant inflammatory profile in patients with asthma was associated with increased severity and duration of rhinovirus infection compared with healthy subjects, supporting the potential role of ILC2s in the pathogenesis of virus-induced asthma exacerbations.
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