Nuocytes are essential in innate type-2 immunity and contribute to the exacerbation of asthma responses. Here we show that nuocytes arise in the bone marrow and differentiate from common lymphoid progenitors, which makes them distinct new members of the lymphoid lineage. Nuocytes required interleukin 7 (IL-7), IL-33 and Notch signalling for development in vitro. Double negative 1 (DN1) and DN2 pro-T-cell progenitors maintained nuocyte potential in vitro, although the thymus was not essential for nuocyte development. Notably, the transcription factor Rorα was critical for nuocyte development and their role in parasitic worm expulsion.

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Interleukin-33 (IL-33) is an IL-1 family cytokine that signals via its receptor T1/ST2, and is a key regulator of inflammation, notably the type-2 response implicated in allergic asthma. Critical to our understanding of the role of IL-33 is the identification of the cellular sources of IL-33. Although progress has been made in this area, the development of a robust live cell reporter of expression would allow the localisation of IL-33 during ongoing immune responses. We have generated a fluorescent reporter mouse line, Il33Cit/+, to define the expression profile of IL-33 in vivo and demonstrate its temporal and spatial expression during experimental allergic asthma responses. We found that type-2 pneumocytes constitute the major source of IL-33 upon allergic lung inflammation following exposure to OVA, fungal extract or ragweed pollen. Using Il33Cit/Cit mice (IL-33-deficient), we establish a role for IL-33 early in the initiation of type-2 responses and the induction of nuocytes (ILC2). We also demonstrate a potential mechanism of action by which IL-33 rapidly initiates type-2 immune responses. Il33Cit/+ mice have enabled new insights into the initiation of type-2 responses and will provide an important tool for further dissection of this important inflammatory pathway in vivo.