title: Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity.
abstract: BACKGROUND
  IL-4, IL-5, and IL-13 are thought to be central to the allergic asthmatic response. Previous work supposed that the essential source of these cytokines was CD4(+) T(H)2 cells. However, more recent studies have suggested that other innate production of type 2 cytokines might be as important.
  
  
  OBJECTIVE
  Nuocytes are a novel population of IL-13-producing innate cells, which are critical for protective immunity in Nippostrongylus brasiliensis infection. Given this, we investigated the potential existence and functional importance of nuocytes in experimental allergic asthma.
  
  
  METHODS
  We generated Il4(+/eGFP)Il13(+/Tomato) dual-reporter mice to study cytokine-producing cells during allergic inflammation. We adoptively transferred innate IL-13-producing cells to investigate their role in airways hyperreactivity (AHR).
  
  
  RESULTS
  We show that allergen-induced nuocytes infiltrate the lung and are a major innate source of IL-13. CD4(+) T cells in the lung almost exclusively express only IL-13, whereas IL-4-producing T cells were restricted to the draining lymph nodes. Intranasal administration of IL-25 or IL-33 induced IL-13-producing nuocytes in the BAL fluid. Strikingly, adoptive transfer of wild-type nuocytes, but not Il13(-/-) nuocytes, into Il13(-/-) mice, which are normally resistant to IL-25-induced AHR, restored airways resistance and lung cell infiltration.
  
  
  CONCLUSIONS
  These findings identify nuocytes as a novel cell type in allergic lung inflammation and an innate source of IL-13 that can directly induce AHR in the absence of IL-13-producing CD4(+) T cells. These data highlight nuocytes as an important new consideration in the development of future allergic asthma therapy.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Barlow
authors.forename: Agustin
authors.initials: A
authors.lastname: Bellosi
authors.forename: Clare S
authors.initials: CS
authors.lastname: Hardman
authors.forename: Lesley F
authors.initials: LF
authors.lastname: Drynan
authors.forename: See Heng
authors.initials: SH
authors.lastname: Wong
authors.forename: James P
authors.initials: JP
authors.lastname: Cruickshank
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018793:Interleukin-13