異なるヘルパーＴ細胞による腸管ＩｇＡの変化と腸内細菌叢への影響の検討

该项目的目的是剖析适应性免疫系统在建立宿主和肠道细菌之间的共生关系中的贡献。我们发现：1)缺乏B细胞、T细胞或两者都缺乏的小鼠不能支持肠道内复杂的细菌群落；2)用表达转录因子Foxp3的CD4+ T细胞重建T细胞缺陷小鼠（Foxp3+ T细胞）可以恢复细菌的多样性和系统发育结构；3) Foxp3+ T细胞有助于梭状芽孢杆菌的多样化，尤其是非毒性梭状芽孢杆菌，最近有报道称它们可以诱导Foxp3。这意味着不仅梭状芽胞杆菌诱导Foxp3，而且Foxp3+ T细胞有助于厚壁菌门梭状芽胞杆菌（小鼠和人类中最多样化的细菌物种）的持久性和多样化；4) Foxp3+ T细胞在生发中心外和生发中心内作用，分别通过预防炎症和调节IgAs的选择；5)需要用选定的IgAs包被细菌，以维持肠道内的细菌，并防止可能成为致病性的机会菌种的扩张。这项研究发表在2014年的《免疫》杂志上。

The aim of the project was to dissect the contribution of the adaptive immune system in establishing the symbiosis between host and bacteria in the gut.We found that: 1) mice deficient for B cells, T cells or both, fail to support complex bacterial communities in the gut; 2) the reconstitution of T cell-deficient mice with CD4+ T cells expressing the transcription factor Foxp3 (Foxp3+ T cells) restores both the diversity and the phylogenetic structure of bacteria; 3) Foxp3+ T cells helped diversification particularly of the non-virulent Clostridia species, which were recently reported to induce Foxp3. This means that not only Clostridia induce Foxp3, but that the Foxp3+ T cells contribute to the persistence and diversification of Clostridia of the Firmicutes (the most diverse bacterial species in both mice and humans); 4) Foxp3+ T cells act outside and inside germinal centers, by preventing inflammation and by regulating selection of IgAs, respectively; 5) the coating of bacteria with selected IgAs was required to maintain the bacteria in the gut and to prevent the expansion of opportunistic species which could become pathogenic.The research was published in Immunity, 2014.