Non-redundant functions of group 2 innate lymphoid cells

Here, we report the generation of a new mouse model based on the Nmur1 promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein (GFP), which allows gene targeting in ILC2 without affecting other innate and adaptive immune cells. By removing Id2 and Gata-3 using Cre-mediated gene deletion in Nmur1-expressing cells, we have generated mice with selective and specific deficiency in ILC2. ILC2-deficient mice have decreased eosinophil counts in steady state and are unable to recruit eosinophils in the airways in models of allergic asthma. Further, ILC2-deficient mice fail to mount an appropriate immune and epithelial type 2 response resulting in a profound defect in worm control and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during diseases and argue for a multilayered organization of the immune system based on a spatiotemporal division of labor. RNA-Sequencing of Eosinophils from the Lung after papain treatment (day7) comparing cKO mice (Nmur1Cre-T2A-GFPId2flox/flox) and littermate controls (Id2flox/flox)