Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
Danone Nutricia Research B.V., 3584 CT Utrecht, The Netherlands.
Biomolecules. 2023 Jan 31;13(2):263. doi: 10.3390/biom13020263.
Proper early life immune development creates a basis for a healthy and resilient immune system, which balances immune tolerance and activation. Deviations in neonatal immune maturation can have life-long effects, such as development of allergic diseases. Evidence suggests that human milk oligosaccharides (HMOS) possess immunomodulatory properties essential for neonatal immune maturation. To understand the immunomodulatory properties of enzymatic or bacterial produced HMOS, the effects of five HMOS (2'FL, 3FL, 3'SL, 6'SL and LNnT), present in human milk have been studied. A PBMC immune model, the IEC barrier model and IEC/PBMC transwell coculture models were used, representing critical steps in mucosal immune development. HMOS were applied to IEC cocultured with activated PBMC. In the presence of CpG, 2'FL and 3FL enhanced IFNγ ( < 0.01), IL10 ( < 0.0001) and galectin-9 ( < 0.001) secretion when added to IEC; 2'FL and 3FL decreased Th2 cell development while 3FL enhanced Treg polarization ( < 0.05). IEC were required for this 3FL mediated Treg polarization, which was not explained by epithelial-derived galectin-9, TGFβ nor retinoic acid secretion. The most pronounced immunomodulatory effects, linking to enhanced type 1 and regulatory mediator secretion, were observed for 2'FL and 3FL. Future studies are needed to further understand the complex interplay between HMO and early life mucosal immune development.
适当的早期生命免疫发育为健康和有弹性的免疫系统奠定了基础，这种免疫系统平衡了免疫耐受和激活。新生儿免疫成熟的偏差可能会产生终身影响，例如过敏疾病的发展。有证据表明，人乳低聚糖（HMO）具有对新生儿免疫成熟至关重要的免疫调节特性。为了了解酶法或细菌产生的 HMO 的免疫调节特性，研究了五种存在于人乳中的 HMO（2'FL、3FL、3'SL、6'SL 和 LNnT）的作用。使用了 PBMC 免疫模型、IEC 屏障模型和 IEC/PBMC Transwell 共培养模型，这些模型代表了黏膜免疫发育的关键步骤。将 HMO 应用于与活化的 PBMC 共培养的 IEC 中。在 CpG 的存在下，2'FL 和 3FL 增强了 IFNγ（<0.01）、IL10（<0.0001）和半乳糖凝集素-9（<0.001）的分泌，当添加到 IEC 中时；2'FL 和 3FL 减少了 Th2 细胞的发育，而 3FL 增强了 Treg 极化（<0.05）。这种 3FL 介导的 Treg 极化需要 IEC，这不能用上皮衍生的半乳糖凝集素-9、TGFβ或视黄酸的分泌来解释。与增强的 1 型和调节介质分泌相关的最显著的免疫调节作用，观察到 2'FL 和 3FL。需要进一步的研究来进一步了解 HMO 和早期生命黏膜免疫发育之间的复杂相互作用。
