Cytokine-mediated regulation of ILC2 development and effector functions against gastrointestinal helminths

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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. During the first funding period of this priority program we could show that the IL-4/IL-13-induced transcription factor STAT6 plays an important role for proliferation and accumulation of ILC2s in the lung of Nb-infected mice. For the second funding period we propose to identify and functionally characterize STAT6-regulated genes in ILC2s. In addition, we will use fluorescent reporter mice to study the migration of ILC2s and their co-localization with other effector cells during helminth infection. Finally, we will specifically delete IL-4/IL-13 in ILC2s to investigate, whether ILC2s are a non-redundant source for both cytokines during primary and secondary immune responses against helminths. Overall, this project will improve our understanding of tissue localization, effector function and plasticity of ILC2s.