Characterization of Allergen Experienced Group 2 Innate Lymphoid Cells: where do they come from, where do they go?

Abstract

Abstract We identified group 2 innate lymphoid cells (ILC2s) in mouse lungs. Upon exposure to the protease allergen papain, lung ILC2s produced large amounts of IL-5 and IL-13 and induced eosinophilia and mucus hyperproduction. Intranasal injections of recombinant IL-33 also stimulated lung ILC2s. ILC2s that were previously stimulated by an allergen persisted long after the initial inflammation was resolved and responded to allergen challenge more vigorously than naïve ILC2s. Microarray analyses of the gene expression profiles of ILC2s isolated from naïve and allergen-treated mice showed that allergen-experienced ILC2s have a similar gene profile to that of memory T cells. To further study the process of “memory ILC2” generation, we analyzed the expression of cell surface molecules on ILC2s from untreated mice and those after intranasal IL-33 injections at various time points, which showed differential expression of CD27, CD103, CD41 and the IL-25 receptor (IL-25R). Memory ILC2s expressed higher level of IL-25R than naïve ILC2s, and intranasal injection of IL-25 stimulated memory, but not naïve, lung ILC2s. Intranasal IL-33 injections also increased ILC2 numbers in the lung draining mediastinal lymph node (mLN), peripheral blood, spleen and liver but not in the intestine or skin. Phenotype analysis of those ILC2s suggested that activated lung ILC2s migrated into mLN and the blood, and some settled in the liver. The results indicated that IL-25-responsive memory ILC2s are generated and persist in the lung as well as in mLN while the role of the latter in allergic lung inflammation induced by intranasal allergen challenge in sensitized mice is yet to be determined.