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

本研究的目的是探讨适应性免疫系统在肠道细菌与宿主之间建立共生关系中的作用，结果发现：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Foxp 3的CD 4 + T细胞重建T细胞缺陷小鼠（Foxp 3 + T细胞）恢复了细菌的多样性和系统发育结构; 3）Foxp 3 + T细胞有助于多样化，特别是最近报道诱导Foxp 3的非毒性梭菌物种。这意味着不仅梭菌诱导Foxp 3，而且Foxp 3 + T细胞有助于厚壁菌门梭菌的持久性和多样化4）Foxp 3 + T细胞分别通过预防炎症和通过调节IgA的选择在生发中心外部和内部起作用; 5）需要用选定的IgA包被细菌，以维持肠道中的细菌，并防止可能成为致病性的机会性物种的扩张。该研究发表在Immunity，2014。

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.