Gastrointestinal helminths infect more than 2 billion people world-wide and cause major socioeconomic problems. The mechanisms of protective immunity against helminths are incompletely understood. Recent studies indicated that type 2 innate lymphoid cells (ILC2s) contribute to protection against the gastrointestinal helminth Nippostrongylus brasiliensis (Nb) in mice. To elucidate molecular mechanisms that regulate ILC2 development, homeostasis and effector functions in steady-state conditions and after Nb infection we will analyze bone marrow chimeric mice in which we modulate the responsiveness of ILC2s to external cytokines using an inducible system. In a similar way we will study the relative contribution of ILC2-derived IL-4/IL-13 for induction of STAT6-regulated genes in epithelial cells and macrophages which both can contribute to protective immunity against Nb. This project will improve the current understanding of ILC2 development, homeostasis and effector functions against helminths.
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