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首页> 外文期刊>Immunity >Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer's Patch T Follicular Helper Cells
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Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer's Patch T Follicular Helper Cells

机译:肠道菌群通过促进淋巴集结T卵泡辅助细胞的分化和迁移来驱动自身免疫性关节炎。

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摘要

Gut microbiota profoundly affect gut and systemic diseases, but the mechanism whereby microbiota affect systemic diseases is unclear. It is not known whether specific microbiota regulate T follicular helper (Tfh) cells, whose excessive responses can inflict antibody-mediated autoimmunity. Using the K/BxN autoimmune arthritis model, we demonstrated that Peyer's patch (PP) Tfh cells were essential for gut commensal segmented filamentous bacteria (SFB)-induced systemic arthritis despite the production of auto-antibodies predominantly occurring in systemic lymphoid tissues, not PPs. We determined that SFB, by driving differentiation and egress of PP Tfh cells into systemic sites, boosted systemic Tfh cell and auto-antibody responses that exacerbated arthritis. SFB induced PP Tfh cell differentiation by limiting the access of interleukin 2 to CD4(+) T cells, thereby enhancing Tfh cell master regulator Bcl-6 in a dendritic cell-dependent manner. These findings showed that gut microbiota remotely regulated a systemic disease by driving the induction and egress of gut Tfh cells.
机译:肠道菌群对肠道和全身性疾病有深远的影响,但微生物群影响全身性疾病的机制尚不清楚。尚不清楚特定的微生物群是否调节T卵泡辅助细胞(Tfh),其过度反应可引起抗体介导的自身免疫。使用K / BxN自身免疫性关节炎模型,我们证明了Peyer's patch(PP)Tfh细胞对于肠道共壁节段性丝状细菌(SFB)诱发的全身性关节炎至关重要,尽管自身抗体的产生主要发生在全身淋巴组织而非PP中。我们确定,SFB通过驱动PP Tfh细胞的分化和向系统性部位的释放,增强了全身性Tfh细胞和自身抗体的反应,从而加剧了关节炎。 SFB通过限制白介素2进入CD4(+)T细胞来诱导PP Tfh细胞分化,从而以树突状细胞依赖性方式增强Tfh细胞主调节剂Bcl-6。这些发现表明,肠道菌群通过驱动肠道Tfh细胞的诱导和流出来远程调节全身性疾病。

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