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

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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Figure 1: IL25 and IL33 induce IL13-producing nuocytes.
Figure 2: IL25 and IL33 have partially redundant roles for nuocyte induction and worm expulsion.
Figure 3: Adoptive transfer of cultured nuocytes into Il17br -/- mice restores an IL25-responsive phenotype.
Figure 4: Adoptive transfer of wild-type nuocytes, but not IL13-deficient nuocytes, restores rapid worm expulsion in N. brasiliensis-infected Il17br -/- mice.

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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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Authors

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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