Induction of Intestinal Th17 Cells by Flagellins From Segmented Filamentous Bacteria
Induction of Intestinal Th17 Cells by Flagellins From Segmented Filamentous Bacteria
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分段丝状细菌鞭毛蛋白诱导肠道 Th17 细胞
DOI：
10.3389/fimmu.2019.02750
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发表时间：
2019-11-22
影响因子：
7.3
通讯作者：
Xiang, Charlie
中科院分区：
文献类型：
--
作者：
Wang, Yanling;Yin, Yeshi;Xiang, Charlie
T辅助细胞(T-helper-17，Th17)是CD4+T细胞的一个亚群，可产生细胞因子IL-17，在保护宿主免受细菌和真菌感染方面发挥重要作用，尤其是在粘膜表面。它们在小肠固有层(SILP)中含量丰富，它们的分化与肠道菌群的定植有关。节段性丝状细菌(SFB)以其独特的能力驱动Th17细胞在小鼠的SI LP中积聚，引起了研究人员的注意。最近的工作强调，SFB利用微生物黏附触发的内吞作用(Mate)将SFB抗原蛋白转移到小肠上皮细胞(SI ECs)，调节宿主免疫动态平衡。然而，SFB的哪些成分参与了这一免疫反应过程仍不清楚。在这里，我们利用各种技术，包括体外和体内的ELISAT、ELISPOT和RNA-SEQ，研究了SFB鞭毛蛋白在Th17细胞诱导中的作用。结果表明，SFB鞭毛蛋白的免疫功能与SFB相似，即在SI LP中诱导产生IL-17和IL-22的CD4+T辅助细胞(Th17细胞)。此外，与IL-17信号通路相关的基因如IL-6、IL-1β、肿瘤坏死因子-α、IL-17A、IL-17F和IL-22的表达显著增加。此外，SFB鞭毛蛋白与肠上皮细胞关系密切，影响肠上皮细胞特异性基因如NOS2、DUOX2、DOXA2、SAA3、TAT和Lcn2的表达。因此，我们认为SFB鞭毛蛋白在SFB诱导肠道Th17细胞的过程中起重要作用。
T-helper-17 (Th17) cells are a subset of CD4+ T cells that can produce the cytokine interleukin (IL)-17 and play vital roles in protecting the host from bacterial and fungal infections, especially at the mucosal surface. These are abundant in the small intestinal lamina propria (SILP) and their differentiation are associated with the colonization of the intestinal flora. Segmented filamentous bacteria (SFB) drew the attention of researchers due to their unique ability to drive the accumulation of Th17 cells in the SI LP of mice. Recent work has highlighted that SFB used microbial adhesion-triggered endocytosis (MATE) to transfer SFB antigenic proteins into small intestinal epithelial cells (SI ECs) and modulate host immune homeostasis. However, which components of SFB are involved in this immune response process remains unclear. Here, we examined the roles of SFB flagellins in Th17 cells induction using various techniques, including ELISA, ELISPOT, and RNA-seq in vitro and in vivo. The results show that the immune function of SFB flagellins is similar to SFB, i.e., induces the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the SI LP. Furthermore, treatment of mice with SFB flagellins lead to a significant increase in the expression of genes associated with the IL-17 signaling pathway, such as IL-6, IL-1β, TNF-α, IL-17A, IL-17F, and IL-22. In addition, SFB flagellins have an intimate relationship with intestinal epithelial cells, influencing the expression of epithelial cell-specific genes such as Nos2, Duox2, Duoxa2, SAA3, Tat, and Lcn2. Thus, we propose that SFB flagellins play a significant role in the involvement of SFB in the induction of intestinal Th17 cells.