Table_2_MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes.xlsx

Proinflammatory type 1 T helper (Th1) cells are enriched in inflamed tissues and contribute to the maintenance of chronic inflammation in rheumatic diseases. Here we show that the microRNA- (miR-) 31 is upregulated in murine Th1 cells with a history of repeated reactivation and in memory Th cells isolated from the synovial fluid of patients with rheumatic joint disease. Knock-down of miR-31 resulted in the upregulation of genes associated with cytoskeletal rearrangement and motility and induced the expression of target genes involved in T cell activation, chemokine receptor– and integrin-signaling. Accordingly, inhibition of miR-31 resulted in increased migratory activity of repeatedly activated Th1 cells. The transcription factors T-bet and FOXO1 act as positive and negative regulators of T cell receptor (TCR)–mediated miR-31 expression, respectively. Taken together, our data show that a gene regulatory network involving miR-31, T-bet, and FOXO1 controls the migratory behavior of proinflammatory Th1 cells.

在炎症组织中，促炎性1型T辅助（Th1）细胞富集，并参与类风湿性疾病慢性炎症的维持。本研究揭示了在小鼠Th1细胞中，具有反复活化史的细胞以及从类风湿关节病患者滑液分离出的记忆Th细胞中，miR-31（微小RNA-31）的表达上调。miR-31的下调导致与细胞骨架重组和运动相关的基因的上调，并诱导参与T细胞活化、趋化因子受体-和整合素信号通路的目标基因的表达。因此，miR-31的抑制导致了反复活化Th1细胞迁移活性的增加。转录因子T-bet和FOXO1分别作为T细胞受体（TCR）介导的miR-31表达的阳性调节者和阴性调节者。综上所述，我们的数据显示，miR-31、T-bet和FOXO1参与的基因调控网络控制了促炎性Th1细胞的迁移行为。