IL-33 mediates reactive eosinophilopoiesis in response to airborne allergen exposure

E. L. Anderson, T. Kobayashi, K. Iijima, K. R. Bartemes, C. C. Chen, Hirohito Kita

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background Exposure to aeroallergens induces eosinophilic airway inflammation in patients with asthma and allergic airway diseases. The circulating number of eosinophils in peripheral blood is relatively small, leading us to hypothesize that bone marrow needs to be engaged quickly to meet the demands of the tissues. Methods To investigate the communication between the lungs and bone marrow, we used acute allergen exposure and airway inflammation models in mice. Gene-deficient mice and cytokine reporter mice as well as in vitro cell culture models were used to dissect the mechanisms. Results Naïve BALB/c mice produced increased numbers of eosinophil precursors and mature eosinophils in the bone marrow when their airways were exposed to a common fungal allergen, Alternaria alternata. Expression of IL-5 and IL-33 increased rapidly in the lungs, but not in the bone marrow. Sera from allergen-exposed mice promoted eosinophilopoiesis in bone marrow cells from naïve mice, which was blocked by anti-IL-5 antibody. Mice deficient in the IL-33 receptor ST2 (i.e., Il1rl1-/- mice) were unable to increase their serum levels of IL-5 and allergen-induced eosinophilopoiesis in the bone marrow after allergen exposure. Finally, group 2 innate lymphoid cells (ILC2s) in the lungs showed robust expression of IL-5 after Alternaria exposure. Conclusions These finding suggests that lung IL-33, through innate activation of ILC2s and their production of IL-5, plays a key role in promoting acute reactive eosinophilopoiesis in the bone marrow when naïve animals are exposed to airborne allergens. Therefore, bone marrow eosinophilopoiesis may be affected by atmospheric environmental conditions.

Original languageEnglish (US)
Pages (from-to)977-988
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number7
StatePublished - Jul 1 2016


  • IL-33
  • IL-5
  • eosinophilopoiesis
  • eosinophils

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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