Cardoso Cristina R, Provinciatto Pauline R, Godoi Dannielle F, Ferreira Beatriz R, Teixeira Gerlinde, Rossi Marcos A, Cunha Fernando Q, Silva João S
School of Medicine of Ribeirão Preto, University of São Paulo, Department of Biochemistry and Immunology, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G593-600. doi: 10.1152/ajpgi.90431.2008. Epub 2009 Jan 8.
Allergies involve a state of immediate hypersensitivity to antigens, including food proteins. The mechanism underlying the initiation and development of allergic responses involves IL-4 that directly induces the differentiation of committed effector Th2 lymphocytes. Although it is clear that Th2 responses play a pivotal role in the development of allergic responses, it remains unclear which mechanisms are involved in the development of the intestinal damages observed in food allergy. Accordingly, this work aimed to study the role of Th2/IL-4-dependent responses in the development of food allergy and intestinal pathology. C57BL/6 wild-type (WT) and IL-4-/- mice were sensitized with peanut proteins, challenged with peanut seeds, and followed for the development of food allergy and intestinal inflammation. Results demonstrated that exposure to peanut seeds led to weight loss in WT but not in IL-4-/- mice that preserved gut integrity with no signs of mucosal inflammation. These animals presented increased levels of IgG2a in sera, suggesting a role for allergic antibodies in the pathogenesis of WT animals. Most importantly, results also showed that lack of IL-4 modulated gut mucosal response in food allergy through diminished expression of TNF-alpha mRNA, increased Th1 IFN-gamma, IL-12p40, regulatory cytokines, and Foxp3, demonstrating their relevance in the control of allergic inflammatory processes, especially in the intestine. Finally, this study highlighted some of the complex mechanisms involved in the pathogenesis of allergic responses to food antigens in the gut, thereby providing valuable tools for directing novel therapeutic or preventive strategies to the control of allergic enteropathy.
过敏反应涉及对包括食物蛋白在内的抗原的速发型超敏反应状态。过敏反应起始和发展的潜在机制涉及白细胞介素-4（IL-4），它直接诱导定向效应性辅助性T2（Th2）淋巴细胞的分化。虽然很明显Th2反应在过敏反应的发展中起关键作用，但食物过敏中观察到的肠道损伤的发展涉及哪些机制仍不清楚。因此，这项工作旨在研究Th2/IL-4依赖性反应在食物过敏和肠道病理发展中的作用。用花生蛋白对C57BL/6野生型（WT）和IL-4基因敲除小鼠进行致敏，用花生种子进行激发，并跟踪食物过敏和肠道炎症的发展情况。结果表明，接触花生种子导致WT小鼠体重减轻，但IL-4基因敲除小鼠体重未减轻，且其肠道完整性得以保持，无黏膜炎症迹象。这些动物血清中IgG2a水平升高，表明过敏抗体在WT动物发病机制中发挥作用。最重要的是，结果还表明，IL-4的缺乏通过降低肿瘤坏死因子-α（TNF-α）mRNA的表达、增加Th1干扰素-γ（IFN-γ）、白细胞介素-12p40、调节性细胞因子和叉头框蛋白3（Foxp3）来调节食物过敏中的肠道黏膜反应，证明它们在控制过敏性炎症过程中具有相关性，尤其是在肠道中。最后，这项研究突出了肠道中对食物抗原过敏反应发病机制中涉及的一些复杂机制，从而为指导控制过敏性肠病的新型治疗或预防策略提供了有价值的工具。
