Humanized mouse model of mast cell–mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis

Paul J Bryce, Rustom Falahati, Laurie L. Kenney, John Leung, Christopher Bebbington, Nenad Tomasevic, Rebecca A. Krier, Chia Lin Hsu, Leonard D. Shultz, Dale L. Greiner, Michael A. Brehm*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background Mast cells are a critical component of allergic responses in humans, and animal models that allow the in vivo investigation of their contribution to allergy and evaluation of new human-specific therapeutics are urgently needed. Objective To develop a new humanized mouse model that supports human mast cell engraftment and human IgE-dependent allergic responses. Methods This model is based on the NOD-scid IL2rgnull SCF/GM-CSF/IL3 (NSG-SGM3) strain of mice engrafted with human thymus, liver, and hematopoietic stem cells (termed Bone marrow, Liver, Thymus [BLT]). Results Large numbers of human mast cells develop in NSG-SGM3 BLT mice and populate the immune system, peritoneal cavity, and peripheral tissues. The human mast cells in NSG-SGM3 BLT mice are phenotypically similar to primary human mast cells and express CD117, tryptase, and FcεRI. These mast cells undergo degranulation in an IgE-dependent and -independent manner, and can be readily cultured in vitro for additional studies. Intradermal priming of engrafted NSG-SGM3 mice with a chimeric IgE containing human constant regions resulted in the development of a robust passive cutaneous anaphylaxis response. Moreover, we describe the first report of a human mast cell antigen-dependent passive systemic anaphylaxis response in primed mice. Conclusions NSG-SGM3 BLT mice provide a readily available source of human mast cells for investigation of mast cell biology and a preclinical model of passive cutaneous anaphylaxis and passive systemic anaphylaxis that can be used to investigate the pathogenesis of human allergic responses and to test new therapeutics before their advancement to the clinic.

Original languageEnglish (US)
Pages (from-to)769-779
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number3
DOIs
StatePublished - Sep 1 2016

Keywords

  • Mast cell
  • NSG
  • NSG-SGM3
  • PCA
  • PSA
  • humanized mice
  • passive cutaneous anaphylaxis
  • passive systemic anaphylaxis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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