Cao Severine, Feehley Taylor J, Nagler Cathryn R
Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, JFK R120, Chicago, IL 60637, United States.
Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, JFK R120, Chicago, IL 60637, United States.
FEBS Lett. 2014 Nov 17;588(22):4258-66. doi: 10.1016/j.febslet.2014.04.026. Epub 2014 May 1.
The prevalence of life-threatening anaphylactic responses to food is rising at an alarming rate. The emerging role of the gut microbiota in regulating food allergen sensitization may help explain this trend. The mechanisms by which commensal bacteria influence sensitization to dietary antigens are only beginning to be explored. We have found that a population of mucosa-associated commensal anaerobes prevents food allergen sensitization by promoting an IL-22-dependent barrier protective immune response that limits the access of food allergens to the systemic circulation. This early response is followed by an adaptive immune response mediated in part by an expansion of Foxp3(+) Tregs that fortifies the tolerogenic milieu needed to maintain non-responsiveness to food. Bacterial metabolites, such as short-chain fatty acids, may contribute to the process through their ability to promote Foxp3(+) Treg differentiation. This work suggests that environmentally induced alterations of the gut microbiota offset the regulatory signals conferred by protective bacterial species to promote aberrant responses to food. Our research presents exciting new possibilities for preventing and treating food allergies based on interventions that modulate the composition of the gut microbiota.
危及生命的食物过敏反应的发生率正以惊人的速度上升。肠道微生物群在调节食物过敏原致敏方面的新作用可能有助于解释这一趋势。共生细菌影响对饮食抗原致敏的机制才刚刚开始被探索。我们发现,一群黏膜相关共生厌氧菌通过促进依赖白细胞介素-22的屏障保护性免疫反应来防止食物过敏原致敏,这种免疫反应限制了食物过敏原进入体循环。这种早期反应之后是适应性免疫反应,部分由Foxp3(+)调节性T细胞的扩增介导,该扩增强化了维持对食物无反应所需的耐受环境。细菌代谢产物,如短链脂肪酸,可能通过促进Foxp3(+)调节性T细胞分化的能力而参与这一过程。这项研究表明,环境诱导的肠道微生物群改变会抵消保护性细菌物种赋予的调节信号,从而促进对食物的异常反应。我们的研究为基于调节肠道微生物群组成的干预措施预防和治疗食物过敏提供了令人兴奋的新可能性。