Altered composition of Innate lymphoid cells in BAL and blood of adult patients with cystic fibrosis towards ILC1

Cystic fibrosis (CF) is a genetic disorder caused by mutations of CFTR gene which affects epithelial cell functions in different organs. It manifests primarily in the lung and leads to severe symptoms. The reduced ciliated-clearance of high viscous mucus leads to chronic infections which in turns alters lung immune responses. Innate lymphoid cells (ILCs) are crucial in the response against pathogens and in tissue homeostasis and their importance has been demonstrated in lung disease such as COPD, but studies ILCs in CF are scarce. In the present study ILCs and their subgroups have been analyzed via flow cytometry in Broncho-alveolar lavage (BAL) (n = 7) and blood (n = 24) of adult CF patients and compared to healthy controls (n = 19). A subdivision into ILC1, 2 and 3 were performed by expression of CD117, CRTH2 and transcriptions factors GATA3 and T-bet. Beside ILC population, cytokine production has been analysed. All data have been compared to clinical data (e.g. FEV1) and correlated to infections with P. aeruginosa or S. aureus. Patients with CF showed a higher proportion of ILC1s in BAL and blood and a reduction in ILC3 fraction. High levels of the ILC1 effector cytokine IFNγ were detected in BAL fluid. Lower levels of blood ILC2s were only detected in patients with chronic P. aeruginosa infections. In contrast, ILC2s in the lung were reduced or completely absent. CF patients with a remaining ILC2 fraction in lung had higher FEV1 levels, compared to those with no ILC2 detectable, indicating an impact of ILC2 on lung homeostasis. In conclusion, the analysis of ILC proportions in CF patients revealed an increased ILC1 fraction in periphery and lung.