IL-33 citrine reporter mice reveal the temporal and spatial expression of IL-33 during allergic lung inflammation

Eur J Immunol. 2013 Feb;43(2):488-98. doi: 10.1002/eji.201242863. Epub 2012 Dec 26.


Interleukin-33 (IL-33) is an IL-1 family cytokine that signals via its receptor T1/ST2, and is a key regulator of inflammation, notably the type-2 response implicated in allergic asthma. Critical to our understanding of the role of IL-33 is the identification of the cellular sources of IL-33. Although progress has been made in this area, the development of a robust live cell reporter of expression would allow the localisation of IL-33 during ongoing immune responses. We have generated a fluorescent reporter mouse line, Il33(Cit/+), to define the expression profile of IL-33 in vivo and demonstrate its temporal and spatial expression during experimental allergic asthma responses. We found that type-2 pneumocytes constitute the major source of IL-33 upon allergic lung inflammation following exposure to OVA, fungal extract or ragweed pollen. Using Il33(Cit/Cit) mice (IL-33-deficient), we establish a role for IL-33 early in the initiation of type-2 responses and the induction of nuocytes (ILC2). We also demonstrate a potential mechanism of action by which IL-33 rapidly initiates type-2 immune responses. Il33(Cit/+) mice have enabled new insights into the initiation of type-2 responses and will provide an important tool for further dissection of this important inflammatory pathway in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / metabolism
  • Fungi / immunology
  • Interleukin-33
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Lung / immunology*
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • Pneumonia / metabolism
  • Pollen / immunology
  • Promoter Regions, Genetic


  • Allergens
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukins