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, IL-5 and IL-13 (ref. 5). T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources remain to be comprehensively elucidated. Here, through the use of novel Il13eGFP reporter mice, we present the identification and functional characterisation 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 IL-25 and IL-33, and represent the predominant early source of IL-13 during helminth infection with Nippostrongylus brasiliensis. In the combined absence of IL-25 and IL-33 signalling, nuocytes fail to expand, resulting in a severe defect in worm expulsion that is rescued by the adoptive transfer of in vitro cultured wildtype, but not IL-13-deficient, nuocytes. Thus, nuocytes represent a critically important innate effector cell in type-2 immunity.

The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed our understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for the human 5q− syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74 – Nid67 interval (containing the Ribosomal protein S14 gene – Rps14) causes macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. This is associated with defective bone marrow progenitor development, increased apoptosis and the appearance of bone marrow cells expressing high levels of p53. Notably, intercrossing with p53-deficient mice, completely rescues the progenitor cell defect, restoring CMP/MEP, GMP and HSC bone marrow populations. This novel mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q− syndrome.

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