Levescot Anais, Cerf-Bensussan Nadine
Laboratory of Intestinal Immunity, INSERM UMR 1163 and Imagine Institute, Université Paris Cité, Paris, France.
Immunol Rev. 2024 Sep;326(1):173-190. doi: 10.1111/imr.13395. Epub 2024 Sep 18.
The critical importance of the immunoregulatory mechanisms, which prevent adverse responses to dietary proteins is demonstrated by the consequences of their failure in two common but distinct human pathological conditions, food allergy and celiac disease. The mechanisms of tolerance to dietary proteins have been extensively studied in mouse models but the extent to which the results in mice can be extrapolated to humans remains unclear. Here, after summarizing the mechanisms known to control oral tolerance in mouse models, we discuss how the monogenic immune disorders associated with food allergy on the one hand, and celiac disease, on the other hand, represent model diseases to gain insight into the key immunoregulatory pathways that control immune responses to food antigens in humans. The spectrum of monogenic disorders, in which the dysfunction of a single gene, is strongly associated with TH2-mediated food allergy suggests an important overlap between the mechanisms that regulate TH2 and IgE responses to food antigens in humans and mice. In contrast, celiac disease provides a unique example of the link between autoimmunity and loss of tolerance to a food antigen.
免疫调节机制对于防止机体对饮食蛋白质产生不良反应至关重要，这一点在两种常见但不同的人类病理状况——食物过敏和乳糜泻中，当其功能失效时所产生的后果中得到了体现。在小鼠模型中，对饮食蛋白质的耐受机制已得到广泛研究，但小鼠实验结果能在多大程度上外推至人类仍不明确。在此，在总结了小鼠模型中已知的控制口服耐受的机制后，我们讨论了一方面与食物过敏相关的单基因免疫疾病，以及另一方面乳糜泻，如何代表了模型疾病，以便深入了解控制人类对食物抗原免疫反应的关键免疫调节途径。单基因疾病谱中，单个基因功能障碍与TH2介导的食物过敏密切相关，这表明在调节人类和小鼠对食物抗原的TH2和IgE反应的机制之间存在重要重叠。相比之下，乳糜泻提供了自身免疫与对食物抗原耐受性丧失之间联系的独特范例。
