A humanized mouse model of anaphylactic peanut allergy

Area of Science:

• Immunology
• Allergy Research
• Gastroenterology

Background:

• Food allergy is a significant and growing health concern with limited therapeutic options.
• Studying human food allergy is challenging due to the scarcity of intestinal tissue and gut immune cells.
• Existing mouse models have limitations in fully recapitulating human immune responses.

Purpose of the Study:

• To develop a mouse model with a humanized adaptive immune system capable of IgE-mediated responses.
• To enable the study of mast cell function in humanized models of food allergy.
• To investigate systemic anaphylaxis triggered by food ingestion in a humanized setting.

Main Methods:

• Generation of humanized mice by engrafting nonobese diabetic severe combined immunodeficient (NSG) mice with human hematopoietic stem cells.
• Assessment of immune responses, mast cell presence, and anaphylaxis following peanut feeding.
• Evaluation of the effect of IgE neutralization (omalizumab) on anaphylactic reactions.

Main Results:

• Humanized NSG mice demonstrated successful engraftment of human T and B lymphocytes and mast cells in tissues, including the gut.
• Mice developed peanut-specific IgE responses after peanut feeding.
• Enteral peanut challenge induced mast cell-mediated systemic anaphylaxis, evidenced by hypothermia and increased tryptase levels.
• Anti-IgE treatment successfully prevented anaphylaxis.

Conclusions:

• Humanized NSG mice serve as a valuable new model for investigating food allergy.
• This model facilitates the study of IgE-mediated anaphylaxis in a humanized context.
• The model allows for the exploration of therapeutic interventions for food allergies.