AMP kinase promotes Bcl6 expression in both mouse and human T cells.
AMP kinase promotes Bcl6 expression in both mouse and human T cells.
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AMP激酶促进小鼠和人T细胞中的BCL6表达。
DOI：
10.1016/j.molimm.2016.11.020
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发表时间：
2017-01
影响因子：
3.6
通讯作者：
Dent AL
中科院分区：
文献类型：
--
作者：
Xie MM;Amet T;Liu H;Yu Q;Dent AL
转录因子Bcl 6是滤泡辅助性T（TFH）细胞的主要调节因子，因此理解诱导Bcl 6和TFH细胞分化的信号通路至关重要。在T细胞活化过程中产生的IL-2抑制Bcl 6表达，但TFH细胞如何逃避IL-2抑制尚不完全清楚。在这里，我们表明，Bcl 6是高度上调的活化的CD 4 T细胞后，葡萄糖剥夺（GD），这条途径是不敏感的抑制IL-2。与GD类似，葡萄糖类似物2-脱氧葡萄糖（2DG）抑制糖酵解，并且2DG诱导活化的CD 4 T细胞中的Bcl 6表达。代谢传感器AMP激酶（AMPK）在糖酵解减少时被激活，并且AMPK拮抗剂化合物C抑制GD对Bcl 6的诱导。此外，药物AICAR激活AMPK导致活化的CD 4 T细胞中Bcl 6上调。当使用AICAR作为佐剂用KLH免疫小鼠时，存在强烈的TFH依赖性增强KLH特异性抗体（Ab）应答，并且体内TFH细胞中Bcl 6表达更高。AMPK的激活强烈诱导BCL 6和人CD 4 T细胞上调TFH细胞标志物表达。我们的数据揭示了TFH细胞分化的主要新途径，由小鼠和人T细胞保守。据报道，成熟的TFH细胞与TH 1细胞相比具有较低的代谢状态。我们的数据表明，降低代谢可能是决定性的TFH细胞分化，而不仅仅是TFH细胞分化的结果。
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells. The metabolic sensor AMP kinase (AMPK) is activated when glycolysis is decreased, and the induction of Bcl6 by GD was inhibited by the AMPK antagonist compound C. Additionally, activation of AMPK by the drug AICAR caused Bcl6 up-regulation in activated CD4 T cells. When mice were immunized with KLH using AICAR as an adjuvant, there was a strong TFH–dependent enhancement of KLH-specific antibody (Ab) responses, and higher Bcl6 expression in TFH cells in vivo. Activation of AMPK strongly induced BCL6 and the up-regulation of TFH cell marker expression by human CD4 T cells. Our data reveal a major new pathway for TFH cell differentiation, conserved by both mouse and human T cells. Mature TFH cells are reported to have a lower metabolic state compared to TH1 cells. Our data indicates that decreased metabolism may be deterministic for TFH cell differentiation, and not simply a result of TFH cell differentiation.
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DOI：
10.1126/science.1176676
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Nurieva RI;Chung Y;Martinez GJ;Yang XO;Tanaka S;Matskevitch TD;Wang YH;Dong C
通讯作者：
Dong C
影响因子：
7
作者：
McHeyzer-Williams LJ;Pelletier N;Mark L;Fazilleau N;McHeyzer-Williams MG
通讯作者：
McHeyzer-Williams MG
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
DOI：
10.1084/jem.20111174
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Johnston RJ;Choi YS;Diamond JA;Yang JA;Crotty S
通讯作者：
Crotty S
DOI：
10.1073/pnas.1301138111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Liao, Wei;Spolski, Rosanne;Leonard, Warren J.
通讯作者：
Leonard, Warren J.