IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation.
IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation.
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DOI：
10.1016/j.celrep.2018.02.044
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发表时间：
2018-03-06
期刊：
影响因子：
8.8
通讯作者：
McGeachy MJ
中科院分区：
文献类型：
--
作者：
Revu S;Wu J;Henkel M;Rittenhouse N;Menk A;Delgoffe GM;Poholek AC;McGeachy MJ
Th17细胞驱动自身免疫性疾病，但也控制共生微生物。来自自身蛋白或共生微生物区系的抗原之间的一个共同联系是T细胞受体(TCR)和共刺激信号的相对较低的激活。事实上，强烈的TCR/CD28刺激抑制了Th17细胞从人类原始T细胞分化而来，但不抑制效应/记忆细胞。CD28抑制经典的Th17转录程序，同时诱导已知的Th17调节因子，并通过Akt依赖的机制发挥作用。没有CD28分化的Th17细胞并不是无能的：它们表现出强劲的增殖能力，并在重新刺激后保持Th17细胞因子的产生。IL-23和IL-1β促进葡萄糖摄取和糖酵解。虽然与CD28共刺激相比略有增加，但糖酵解是支持Th17分化所必需的，这表明细胞因子介导的代谢变化足以消除Th17分化中对CD28的经典要求。综上所述，这些数据表明，在人类中，TcR/CD28/Akt的激活强度是调节IL-23和IL-1β驱动的Th17发育的变阻器。CD28共刺激被认为是T细胞激活、驱动有氧糖酵解和预防无能所必需的“信号2”。Revu等人。研究发现，对于人类Th17细胞，IL-23和IL-1β为代谢增加和避免无能提供了足够的信号，而CD28共刺激抑制了Th17转录程序的诱导。
Th17 cells drive autoimmune disease but also control commensal microbes. A common link among antigens from self-proteins or commensal microbiota is relatively low activation of T cell receptor (TCR) and costimulation signaling. Indeed, strong TCR/CD28 stimulation suppressed Th17 cell differentiation from human naive T cells, but not effector/memory cells. CD28 suppressed the classical Th17 transcriptional program, while inducing known Th17 regulators, and acted through an Akt-dependent mechanism. Th17 cells differentiated without CD28 were not anergic: they showed robust proliferation and maintained Th17 cytokine production following re-stimulation. Interleukin (IL)-23 and IL-1β promoted glucose uptake and increased glycolysis. Although modestly increased compared to CD28 costimulation, glycolysis was necessary to support Th17 differentiation, indicating that cytokine-mediated metabolic shifts were sufficient to obviate the classical requirement for CD28 in Th17 differentiation. Together, these data propose that, in humans, strength of TCR/CD28/Akt activation serves as a rheostat tuning the magnitude of Th17 development driven by IL-23 and IL-1β. CD28 costimulation is considered the requisite “signal 2” for T cell activation, driving aerobic glycolysis and preventing anergy. Revu et al. find that, for human Th17 cells, IL-23 and IL-1β provide sufficient signals for metabolic increases and avoidance of anergy, whereas CD28 costimulation suppresses induction of the Th17 transcriptional program.
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DOI：
10.4049/jimmunol.1402554
发表时间：
2015-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hawse WF;Sheehan RP;Miskov-Zivanov N;Menk AV;Kane LP;Faeder JR;Morel PA
通讯作者：
Morel PA
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
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
影响因子：
4.1
作者：
Annunziato, Francesco;Cosmi, Lorenzo;Romagnani, Sergio
通讯作者：
Romagnani, Sergio
影响因子：
32.4
作者：
Esensten JH;Helou YA;Chopra G;Weiss A;Bluestone JA
通讯作者：
Bluestone JA