Phenotype and function of innate lymphoid cells in a murine model of impaired muco-ciliary clearance challenged with allergen

Abstract

Despite the known role of innate lymphoid cells as promoters of pulmonary inflammation in various lung diseases, the understanding of their involvement in conditions of impaired muco-ciliary clearance and the pathogenesis of cystic fibrosis (CF) remains incomplete. In the study presented here, we analysed ILCs in mice with over-expression of the sodium-channel ßENaC, which display a CF-like pulmonary disease phenotype with reduced muco-ciliary clearance and enhanced airway inflammation. We challenged juvenile and adult ßENaC and wild type (WT) mice intra-tracheally with Aspergillus fumigatus (A.f.) extract and compared frequencies and cytokine-production of ILC subpopulations by flow cytometry.

Our research indicates that the response to A.f. is age- and muco-ciliary clearance dependent. In contrast to juvenile WT mice, juvenile ßENaC mice showed increased percentages of effector cytokines interleukin (IL)-5 and IL-13 together with the type 2 innate lymphoid cells. Allergic responses evaluated by BAL differential count and airway eosinophilia was stronger in both, juvenile and adult ßENaC mice compared to WT mice. These data support the previous studies that impaired allergen clearance correlates with the increased levels of innate type-2 lymphoid cells (ILC2) in juvenile ßENaC mice.

Future experiments in ßENaC/RAG^−/− vs. ßENaC mice will interrogate the contribution of ILC2s to the exaggerated type-II inflammation observed in ßENaC mice. Understanding the contribution of ILC2s in this age-dependent process contributes to the dissection of age- and muco-ciliary clearance-dependent inflammatory pathways, which apply to pulmonary diseases beyond CF.