He Y, Liu S, Leone S, Newburg D S
Program in Glycobiology, Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA.
Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Mucosal Immunol. 2014 Nov;7(6):1326-39. doi: 10.1038/mi.2014.20. Epub 2014 Apr 2.
The immature neonatal intestinal immune system hyperreacts to newly colonizing unfamiliar bacteria. The hypothesis that human milk oligosaccharides from colostrum (cHMOSs) can directly modulate the signaling pathways of the immature mucosa was tested. Modulation of cytokine immune signaling by HMOSs was measured ex vivo in intact immature (fetal) human intestinal mucosa. From the genes whose transcription was modulated by cHMOSs, Ingenuity Pathway Analysis identified networks controlling immune cell communication, intestinal mucosal immune system differentiation, and homeostasis. cHMOSs attenuate pathogen-associated molecular pattern-stimulated acute phase inflammatory cytokine protein levels (interleukin-8 (IL-8), IL-6, monocyte chemoattractant protein-1/2 and IL-1β), while elevating cytokines involved in tissue repair and homeostasis. In all, 3'-, 4-, and 6'-galactosyllactoses of cHMOSs account for specific immunomodulation of polyinosinic:polycytodylic acid-induced IL-8 levels. cHMOSs attenuate mucosal responses to surface inflammatory stimuli during early development, while enhancing signals that support maturation of the intestinal mucosal immune system.
新生儿未成熟的肠道免疫系统会对新定植的陌生细菌产生过度反应。我们对初乳中含有的母乳低聚糖（cHMOSs）能够直接调节未成熟黏膜信号通路这一假说进行了验证。在完整的未成熟（胎儿）人肠黏膜中对离体条件下HMOSs对细胞因子免疫信号的调节作用进行了测定。通过对受cHMOSs调控转录的基因进行分析，Ingenuity通路分析确定了控制免疫细胞通讯、肠黏膜免疫系统分化和稳态的网络。cHMOSs可降低病原体相关分子模式刺激引起的急性期炎性细胞因子蛋白水平（白细胞介素-8（IL-8）、IL-6、单核细胞趋化蛋白-1/2和IL-1β），同时提高参与组织修复和稳态的细胞因子水平。cHMOSs的3'-、4-和6'-半乳糖乳糖可特异性调节聚肌苷酸：聚胞苷酸诱导的IL-8水平。cHMOSs在早期发育过程中可减轻黏膜对表面炎性刺激的反应，同时增强支持肠黏膜免疫系统成熟的信号。
