Pulmonary Innate Lymphoid Cell Responses During Rhinovirus-Induced Asthma Exacerbations

RATIONALE: Preclinical models show that type 2 innate lymphoid cells (ILC2) produce type 2 cytokines, while type 1 ILCs (ILC1) produce IFNγ. Analogous ILC populations have been identified in man; however, the role of ILCs during viral exacerbations of asthma is unknown. This study aimed to characterise pulmonary ILC responses in asthma during experimental rhinovirus infection.

METHODS: Patients with moderate–severe asthma and healthy volunteers were inoculated with rhinovirus-16 and underwent bronchoscopy at baseline, and Days 3 and 8 post inoculation. Pulmonary ILC1s and ILC2s were sorted from bronchoalveolar lavage by FACs.

RESULTS: At baseline, ILC2s were increased in patients with asthma vs healthy volunteers (P<0.05), with no difference in ILC1 levels. In asthma, there was a significant increase in ILC2s at Day 8 from baseline (P<0.05). ILC2s at Day 8 were significantly greater in asthma vs healthy volunteers (P<0.05). In healthy volunteers, there was an early increase in ILC1s at Day 3 (P<0.001), whereas in asthma, there was a delayed increase in ILC1s at Day 8 (P<0.05). Patients with asthma had a significantly higher ratio of ILC2:ILC1 at baseline (P<0.05) and Day 8 (P<0.01), with a similar trend observed at Day 3 (P=0.059). Increased ILC2:ILC1 ratio in asthma correlated with clinical markers of exacerbation severity and type 2 cytokines.

CONCLUSIONS: This is the first study to show increased ILC2 recruitment in the lower airways during rhinovirus infection in asthma and delayed ILC1 recruitment compared with healthy volunteers. These results indicate that an ILC2-predominant inflammatory profile is associated with increased severity and duration of respiratory viral infections in asthma.