关键词: CP: Immunology CP: Metabolism CX3CR1(+) cells allergy dendritic cells fasting food antigens mTOR signaling metabolic rewiring nutrition oral tolerance regulatory T cells

Mesh : Animals Arginine / metabolism Immune Tolerance T-Lymphocytes, Regulatory / immunology Ovalbumin / immunology Dendritic Cells / immunology metabolism Mice TOR Serine-Threonine Kinases / metabolism Mice, Inbred C57BL Administration, Oral CX3C Chemokine Receptor 1 / metabolism Intestines / immunology Antigens, CD / metabolism Integrin alpha Chains / metabolism Sugars / metabolism Glycolysis Fasting Signal Transduction Intestinal Mucosa / immunology metabolism Female

来  源:   DOI:10.1016/j.celrep.2024.114490

Abstract:
Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.
摘要:
尽管口服耐受性是调节过敏性疾病的关键系统,饮食因素调节口服耐受诱导和维持的机制尚不清楚.为了解决这个问题,我们探讨了口服卵清蛋白(OVA)给药前在空腹和随意喂食条件下肠道免疫系统中各种免疫细胞的分化和功能.空腹缓解OVA特异性Treg扩张,这对于口服耐受诱导是必不可少的。这种异常主要是由于CX3CR1细胞中的功能缺陷,这些细胞负责腔OVA的摄取和致耐受性CD103树突状细胞的减少。最终,禁食会损害口服OVA对哮喘和过敏性鼻炎发展的预防作用。特定的食物成分,即碳水化合物和精氨酸,通过激活糖酵解和mTOR信号传导对口服耐受诱导是必不可少的。总的来说,先前的食物摄入和营养信号对于通过诱导对摄入的食物抗原的耐受性来维持免疫稳态至关重要。
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