Nuocytes Represent a New Innate Effector Leukocyte That Mediates Type-2 Immunity

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. Here, a new type of innate effector leukocyte cell — the nuocyte — is described and characterized. It is shown that interleukin (IL)25 and IL33 drive the expansion of the nuocyte population, that these cells secrete IL13, and that they are required for protection against helminth infection. 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.