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Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity - Nature

  • ️McKenzie, Andrew N. J.
  • ️Thu Apr 01 2010
  • Letter
  • Published: 01 April 2010

Nature volume 464, pages 1367–1370 (2010)Cite this article

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Abstract

Innate immunity provides the first line of defence against invading pathogens and provides important cues for the development of adaptive immunity. Type-2 immunity—responsible for protective immune responses to helminth parasites1,2 and the underlying cause of the pathogenesis of allergic asthma3,4—consists of responses dominated by the cardinal type-2 cytokines interleukin (IL)4, IL5 and IL13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively determined. Here, through the use of novel Il13-eGFP reporter mice, we present the identification and functional characterization of a new innate type-2 immune effector leukocyte that we have named the nuocyte. Nuocytes expand in vivo in response to the type-2-inducing cytokines IL25 and IL33, and represent the predominant early source of IL13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL25 and IL33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wild-type, but not IL13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.

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Acknowledgements

We thank members of the McKenzie laboratory for their comments on the manuscript. We thank D. Cousins for assistance with preliminary microarray analysis. R.J.F. was supported by Asthma UK. P.G.F. is supported by Science Foundation Ireland.

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Author notes

  1. Daniel R. Neill, See Heng Wong and Agustin Bellosi: These authors contributed equally to this work.

Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK ,

    Daniel R. Neill, See Heng Wong, Agustin Bellosi, Robin J. Flynn, Maria Daly, Theresa K. A. Langford, Richard Pannell, Helen E. Jolin & Andrew N. J. McKenzie

  2. Immunology Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, Pennsylvania 19087, USA ,

    Christine Bucks & Colleen M. Kane

  3. Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland

    Padraic G. Fallon

Authors

  1. Daniel R. Neill

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  2. See Heng Wong

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  3. Agustin Bellosi

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  4. Robin J. Flynn

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  5. Maria Daly

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  6. Theresa K. A. Langford

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  7. Christine Bucks

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  8. Colleen M. Kane

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  9. Padraic G. Fallon

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  10. Richard Pannell

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  11. Helen E. Jolin

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  12. Andrew N. J. McKenzie

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Contributions

D.R.N., S.H.W. and A.B. performed experiments, interpreted data, provided intellectual input and wrote the paper; R.J.F. and T.K.A.L. performed the infection studies; M.D. performed cell isolation studies; C.B. and C.M.K. performed microarray studies and Luminex; P.G.F. provided reagents and intellectual input; R.P. and H.E.J. provided reagents and experimental assistance; A.N.J.M. conceived the study and wrote the paper.

Corresponding author

Correspondence to Andrew N. J. McKenzie.

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Competing interests

S.H.W. and A.N.J.M. were supported by a grant from Centocor.

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Neill, D., Wong, S., Bellosi, A. et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464, 1367–1370 (2010). https://doi.org/10.1038/nature08900

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  • Received: 01 December 2009

  • Accepted: 12 February 2010

  • Published: 01 April 2010

  • Issue Date: 29 April 2010

  • DOI: https://doi.org/10.1038/nature08900

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Editorial Summary

Innate immunity: two lines of defence

Type-2 immunity, the ancient defence mechanism that provides protection against gastrointestinal helminth infections, involves the recruitment of T helper (TH) cells that produce immune mediators or cytokines to coordinate an immune response involving IgE antibody production, the recruitment of eosinophils and goblet cell hyperplasia. Two groups reporting in this issue have characterized innate type 2 effector leukocyte populations that promote TH2 cytokine responses. Saenz et al. describe multipotent progenitor type-2 (MPPtype2) cells that accumulate in response to the cytokine IL-25 (interleukin-25) and give rise to macrophage or granulocyte lineages promoting TH2 differentiation. Neill et al. describe 'nuocytes', induced by IL25 and IL33, which are the predominant early source of IL13 during a helminth infection. In News & Views, Gérard Eberl discusses how these two papers — and a third in Nature Reviews Immunology (http://go.nature.com/sJ9D77) — influence current thinking on the role of innate immunity.

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