3型天然淋巴样细胞通过调控Akkermansia影响病原体感染的机制研究

ILC3s (Group 3 innate lymphoid cells) are rare presence but enrichment in mucosa, especially in the intestinal mucosa, play an important role in pathogens defence. In previous work, we have demonstrated that ILC3s regulate microbiota in intestine by producing IL-22 in Id2 dependence, in turn to resist colonization of Citrobacter rodentium. For further study, we have analyzed several symbiotic bacteria presence in the mucus from ILC3s deficient mice compared with wild-type mice by 16s rRNA sequencing, and found out that Akkermansia increased in the mucus of ILC3s deficient mice. In vivo, we have observed that Akkermansia could aggravate the infection of Citrobacter rodentium. Thus, we hypothesize that ILC3s could suppress colonization and infection of pathogens by regulating Akkermansia. We plan to study how ILC3s regulate Akkermansia and how Akkermansia impacts to defense pathogens, in order to find out novel prebiotics for clinical treatment.

3型天然淋巴样细胞（ILC3s）是最近发现的一群数量极少却富集于黏膜区域（尤其是肠道黏膜区域）并发挥重要作用的天然免疫细胞。我们之前已经报导ILC3s可以通过分泌IL-22调节肠道菌群微生态，进而抵抗肠道病原菌枸橼酸杆菌（Citro）的定植感染，但具体机制尚不清楚。前期实验证明与野生型小鼠相比，ILC3s缺陷小鼠肠道黏膜菌群中Akkermansia菌比例增加，进一步的体内实验证明Akkermansia能够加重小鼠Citro感染，因此我们假设ILC3s可以通过调节Akkermansia的定植影响病原菌的感染。本课题将通过动物模型和体外实验进一步研究ILC3s是如何调节Akkermansia以及Akkermansia是如何影响病原菌的定植和侵袭，这不仅对揭示机体微生态在生理病理中作用机制有重要意义，而且还将为发展新的有效益生菌提供更安全的理论依据。

以往的研究报道ILC3s可以通过分泌IL-22调节肠道菌群微生态，进而抵抗肠道病原菌枸橼酸杆菌（Citro）的定植感染。我们通过16s rRNA测序发现ILC3s缺陷小鼠肠道黏膜菌群中Akkermansia比例增加，进一步的体内实验证明Akkermansia能够加重小鼠Citro感染。通过对Akkermansia代谢产物组学分析，发现其中丁二酸可以发挥促进Citro生长且提升Citro毒力的作用。IL-22的缺失对肠道黏液半乳糖基化修饰水平具有显著调节作用，而半乳糖能够作为Akkermansia的营养来源维持其生长增殖。该研究不仅对揭示机体微生态在生理病理中作用机制有重要意义，而且还将为发展新的有效益生菌提供更安全的理论依据。