Differential regulation of type 2 innate lymphoid cells by IL-25 and IL-33 (P6254)

Abstract

Abstract Type 2 Innate Lymphoid Cells (ILC2s) are a novel innate cell populations that plays important roles in Th2-type immune response. They are lineage-negative, CD44+ and require IL-7 signal during their development. ILC2s produce type 2 cytokines in response to IL-33 in vitro. Animal studies demonstrated the production of type 2 cytokines by ILC2s after intranasal administration of IL-33. In addition to IL-33, IL-25 is also able to stimulate ILC2s to secret type 2 cytokines. However, detail mechanism to explain how ILC2s response to IL-33 and IL-25 has been unknown. The goal of this project is to examine the roles of IL-33 and IL-25 in proliferation and activation of ILC2s. We cultured lung cells with IL-33+IL-7 or IL-25+IL-7 and examined the production of IL-5 and IL-13. Lung ILC2s produced a large quantity of IL-13, but little IL-5 and highly expressed ICOS and ST2 in response to IL-25+IL-7 in vitro. When incubated with IL-33, the majority of ILC2s secreted both IL-5 and IL-13 and expressed intermediate level of ICOS and ST2. When IL-25 was administered intranasally to IL-13-GFP mice, a large proportion of ILC2s highly expressed IL-13-GFP. When IL-33 was administered, ILC2s showed modest expression of IL-13-GFP. These findings suggest that IL-33 and IL-25 are involved in overlapping but maybe different immunological and pathological process.