Nuocytes: new cells in type-2 immune responses
Wednesday 20 October 2010, 12.15PM
Speaker: Dr Andrew McKenzie, MRC Laboratory of Mollecular Biology, University of Cambridge
Type-2 immunity – responsible for protective immune responses to helminth parasites and the underlying cause of the pathogenesis of allergic asthma – consists of responses dominated by the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13. T cells are an important source of these cytokines in adaptive immune responses, but the innate cell sources of IL-13 remain to be comprehensively elucidated. We have used novel /Il13eGFP/ reporter mice to identify IL-13 producing cells during ongoing immune responses. We found that a new innate type-2 immune effector leukocyte that we have named the nuocyte is a major source of IL-13. Nuocytes expand /in vivo/ in response to the type 2-inducing cytokines IL-25 and IL-33, and represent a major 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. We have gone on to show that nuocytes also arise in experimental asthma models and are capable of inducing airways hyperreactivity and cell infiltration into the lungs. Our results suggest that nuocytes fulfill an important role in type-2 immunity.