A humanized mouse model of anaphylactic peanut allergy

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• 作者：Oliver T. Burton ; PhD^a ; ^b ; ^{oliver.burton@childrens.harvard.edu} ; Amanda J. Stranks ; PhD^a ; ^b ; Jaciel M. Tamayo ; PhD^a ; ^b ; Kyle J. Koleoglou ; BA^a ; Lawrence B. Schwartz ; MD ; PhD^c ; Hans C. Oettgen ; MD ; PhD^a ; ^b
• 关键词：IgE ; mast cells ; anaphylaxis ; humanized mice ; tryptase ; peanut allergy
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：139
• 期：1
• 页码：314-322.e9
• 全文大小：4416 K
• 卷排序：139

文摘

Food allergy is a growing health problem with very limited treatment options. Investigation of the immunologic pathways underlying allergic sensitization to foods in humans has been greatly constrained by the limited availability of intestinal tissue and gut-resident immune cells. Although mouse models have offered insights into pathways of food sensitization, differences between rodent and human immune physiology limit the extension of these findings to our understanding of human disease.ObjectiveWe sought to develop a strategy for the generation of mice with humanized adaptive immune systems, complete with tissue engraftment by human mast cells that are competent to mount specific IgE-mediated responses and drive systemic anaphylaxis on ingestion challenge.MethodsNonobese diabetic severe combined immunodeficient mice lacking the cytokine receptor common gamma chain (γc−/−) and carrying a human stem cell factor transgene were engrafted with human hematopoietic stem cells. The impact of peanut (PN) feeding and IgE neutralization on the development of immune responses, mast cell homeostasis, and anaphylactic food allergy was assessed in these animals.ResultsHumanized nonobese diabetic severe combined immunodeficient common gamma chain–deficient stem cell factor (huNSG) mice exhibited robust engraftment with functional human T and B lymphocytes and human mast cells were found in significant numbers in their tissues, including the intestinal mucosa. Following gavage feeding with PN, they mounted specific antibody responses, including PN-specific IgE. When enterally challenged with PN, they exhibited mast-cell–mediated systemic anaphylaxis, as indicated by hypothermia and increases in plasma tryptase levels. Anti-IgE (omalizumab) treatment ablated this anaphylactic response.ConclusionshuNSG mice provide a novel tool for studying food allergy and IgE-mediated anaphylaxis.