饮食中的人乳低聚糖通过调节 SCFAs 水平和 ILC2 活性来减轻过敏性气道炎症。
Dietary human milk oligosaccharides reduce allergic airway inflammation by modulating SCFAs level and ILC2 activity.
机构信息
Department of Clinical laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
出版信息
Immunology. 2024 Nov;173(3):562-574. doi: 10.1111/imm.13845. Epub 2024 Aug 6.
Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or Alternaria alternata in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.
2 型固有淋巴细胞(ILC2s)在哮喘的进展中起着至关重要的作用,但调节 ILC2 反应的机制在哮喘中仍未得到充分探索。人乳寡糖(HMOs)是母乳中重要的非营养成分,已知其可显著影响免疫系统的发育,并影响过敏性疾病的发生。然而,它们对 ILC2 驱动的哮喘的影响尚未完全了解。我们的研究表明,膳食 HMOs 可作为 ILC2 反应和过敏性气道炎症的有效抑制剂。用 2'-岩藻糖基乳糖(2'-FL)和 6'-唾液酸乳糖(6'-SL)治疗可显著减轻木瓜蛋白酶或Alternaria alternata诱导的小鼠 ILC2 相关气道炎症,表现在 BALF 中嗜酸性粒细胞(EOS)浸润减少和 IL-5、IL-13 水平降低。值得注意的是,虽然 ILC2 表达 HMO 受体,但 HMO 并非直接作用于 ILC2,而是通过改变肠道微生物群衍生的 SCFAs 来调节其活性。HMO 治疗以 SCFA 依赖的方式缓解气道炎症,而 SCFA 耗竭或受体阻断则逆转了这些有益作用。这项研究揭示了膳食 HMO 通过调节 ILC2 活性和肠-肺轴在管理哮喘中的潜力,提出了一种利用营养成分的免疫调节能力来治疗呼吸道疾病的新治疗途径。