Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
1] Institute for Research in Biomedicine, Università della Svizzera italiana, via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland [2] Institute of Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Nat Commun. 2015 Mar 16;6:6431. doi: 10.1038/ncomms7431.
T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a regulates responses to cognate antigens through modulation of ERK phosphorylation. By enhancing the signalling cascade from the T-cell receptor, such molecular network reduces the threshold of TH17 cell activation. Moreover, at a late time point, the same network induces a self-regulatory mechanism dependent on ID3, a negative regulator of transcription factors that control RORC expression, thus modulating TH17 activity. Our results demonstrate that the phenotype acquired by TH cells during priming contributes to their threshold of activation to secondary antigenic stimulations, thus influencing memory responses.
T 辅助（TH）细胞在初始阶段的极化受多种信号调节，但极化到特定表型是否也会影响记忆 TH 细胞的回忆反应相对未知。在这里，我们表明 miR-181a 在人类和小鼠幼稚 T 细胞分化为 TH17 细胞，但不是 TH1 或 TH2 亚群时被选择性诱导。在人类记忆 TH17 细胞中，miR-181a 通过调节 ERK 磷酸化来调节对同源抗原的反应。通过增强 T 细胞受体的信号级联反应，这种分子网络降低了 TH17 细胞激活的阈值。此外，在稍后的时间点，相同的网络诱导一种依赖 ID3 的自我调节机制，ID3 是控制 RORC 表达的转录因子的负调节剂，从而调节 TH17 活性。我们的结果表明，TH 细胞在初始阶段获得的表型有助于其对二次抗原刺激的激活阈值，从而影响记忆反应。
