Nuocytes are essential in innate type 2 immunity and contribute to the exacerbation of asthma responses. Here we found that nuocytes arose in the bone marrow and differentiated from common lymphoid progenitors, which indicates they are distinct, previously unknown members of the lymphoid lineage. Nuocytes required interleukin 7 (IL-7), IL-33 and Notch signaling for development in vitro. Pro-T cell progenitors at double-negative stage 1 (DN1) and DN2 maintained nuocyte potential in vitro, although the thymus was not essential for nuocyte development. Notably, the transcription factor RORα was critical for the development of nuocytes and their role in the expulsion of parasitic worms.
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We thank S. Bell for critical reading of the manuscript; A. Corcoran (Babraham Institute) for IL-7Rα-deficient mice; M. Turner and E. Vigorito (Babraham Institute) for B6/SJL mice; J.C. Zuniga-Pflucker (University of Toronto) for OP9-DL1 cells; T. Honjo (Kyoto University) for mice with loxP-flanked alleles encoding Rbpjκ; M. Daly for flow cytometry and J. Cruickshank and the staff of the animal facility for experimental support. Supported by Centocor (S.H.W., J.L.B. and A.N.J.M.), the American Asthma Foundation (J.A.W.), Science Foundation Ireland (P.G.F.), the National Children's Research Centre (P.G.F.), the Medical Research Council (A.N.J.M.) and the American Asthma Foundation (A.N.J.M.).
S.H.W., J.L.B. and A.N.J.M. received support from Centocor.
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Wong, S., Walker, J., Jolin, H. et al. Transcription factor RORα is critical for nuocyte development. Nat Immunol 13, 229–236 (2012). https://doi.org/10.1038/ni.2208
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