Molecular evidence of Group 1 innate lymphoid cell activation in the U-BIOPRED cohort

Background: The Group 1 innate lymphoid cell (Gp 1 ILC), which includes ILC1 and natural killer (NK) cells, express T-bet and IFNγ, and are cytotoxic. Their role in asthma is unclear. Aim: Explore the enrichment of ILC1, ILC2, ILC3 and NK activation signatures in asthmatic transcriptomic samples. Methods: U-BIOPRED participants were classified as moderate to severe asthma eosinophilic, neutrophilic, mixed and paucigranulocytic, based on sputum cell counts, and healthy. We applied Gene Set Variation Analysis to sputum, nasal, bronchial brush and bronchial biopsies using published signatures [Bjorklund et al. Nat Immunol 2016,17:451-60]. Results: ILC1 but not ILC2 or ILC3 ES were higher in non-smoking severe sputum, particularly in neutrophilic and mixed patients. This phenotype has been associated with inflammasome, IFNγ and TNF activation [Kuo at al. Eur Respir J.2017, 49, in press]. In eosinophilic asthma, ILC1 ES was lower, ILC2 higher and ILC3 similar across groups (Fig1A). ILC1 and NK ES correlated with M1 macrophage signature in all compartments (Fig1B). ILC2 ES correlated with M2 macrophage signature, except in nasal brush. Conclusion: A neutrophilic severe asthma phenotype has been characterized by Group 1 ILC activation, associated with inflammasome, IFNγ, and TNF, which may reflect an antimicrobial response and contribute to chronic inflammation and remodelling in severe asthma.