Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice

Ryoji Ito, Takeshi Takahashi, Ikumi Katano, Kenji Kawai, Tsutomu Kamisako, Tomoyuki Ogura, Miyuki Ida-Tanaka, Hiroshi Suemizu, Satoshi Nunomura, Chisei Ra, Akio Mori, Sadakazu Aiso, Mamoru Ito

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63 Citations (Scopus)

Abstract

The development of animal models that mimic human allergic responses is crucial to study the pathophysiology of disease and to generate new therapeutic methodologies. Humanized mice reconstituted with human immune systems are essential to study human immune reactions in vivo and are expected to be useful for studying human allergies. However, application of this technology to the study of human allergies has been limited, largely because of the poor development of human myeloid cells, especially granulocytes and mast cells, which are responsible for mediating allergic diseases, in conventional humanized mice. In this study, we developed a novel transgenic (Tg) strain, NOD/Shi-scid-IL2rgnull (NOG), bearing human IL-3 and GM-CSF genes (NOG IL-3/GM-Tg). In this strain, a large number of human myeloid cells of various lineages developed after transplantation of human CD34+ hematopoietic stem cells. Notably, mature basophils and mast cells expressing FcRI were markedly increased. These humanized NOG IL-3/GM-Tg mice developed passive cutaneous anaphylaxis reactions when administered anti-4-hydroxy-3- nitrophenylacetyl IgE Abs and 4-hydroxy-3-nitrophenylacetyl. More importantly, a combination of serum from Japanese cedar pollinosis patients and cedar pollen extract also elicited strong passive cutaneous anaphylaxis responses in mice. Thus, to our knowledge, our NOG IL-3/ GM-Tg mice are the first humanized mouse model to enable the study of human allergic responses in vivo and are excellent tools for preclinical studies of allergic diseases.

Original languageEnglish
Pages (from-to)2890-2899
Number of pages10
JournalJournal of Immunology
Volume191
Issue number6
DOIs
Publication statusPublished - 2013 Sep 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ito, R., Takahashi, T., Katano, I., Kawai, K., Kamisako, T., Ogura, T., Ida-Tanaka, M., Suemizu, H., Nunomura, S., Ra, C., Mori, A., Aiso, S., & Ito, M. (2013). Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice. Journal of Immunology, 191(6), 2890-2899. https://doi.org/10.4049/jimmunol.1203543