Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Cells. 2020 Jul 17;9(7):1716. doi: 10.3390/cells9071716.
Activation and subsequent differentiation of T cells following antigenic stimulation are triggered by highly coordinated signaling events that lead to instilling cells with a discrete metabolic and transcriptional feature. Compelling studies indicate that intracellular nicotinamide adenine dinucleotide (NAD) levels have profound influence on diverse signaling and metabolic pathways of T cells, and hence dictate their functional fate. CD38, a major mammalian NAD glycohydrolase (NADase), expresses on T cells following activation and appears to be an essential modulator of intracellular NAD levels. The enzymatic activity of CD38 in the process of generating the second messenger cADPR utilizes intracellular NAD and thus limits its availability to different NAD consuming enzymes (PARP, ART, and sirtuins) inside the cells. The present review discusses how the CD38-NAD axis affects T cell activation and differentiation through interfering with their signaling and metabolic processes. We also describe the pivotal role of the CD38-NAD axis in influencing the chromatin remodeling and rewiring T cell response. Overall, this review emphasizes the crucial contribution of the CD38NAD axis in altering T cell response in various pathophysiological conditions.
抗原刺激后 T 细胞的激活和随后的分化是由高度协调的信号事件触发的，这些信号事件使细胞获得离散的代谢和转录特征。有说服力的研究表明，细胞内烟酰胺腺嘌呤二核苷酸（NAD）水平对 T 细胞的多种信号和代谢途径有深远影响，因此决定了它们的功能命运。CD38 是一种主要的哺乳动物 NAD 糖水解酶（NADase），在 T 细胞激活后表达，并似乎是细胞内 NAD 水平的重要调节剂。CD38 在生成第二信使 cADPR 的过程中的酶活性利用细胞内 NAD，从而限制其在细胞内不同的 NAD 消耗酶（PARP、ART 和 sirtuins）中的可用性。本综述讨论了 CD38-NAD 轴如何通过干扰 T 细胞的信号和代谢过程来影响 T 细胞的激活和分化。我们还描述了 CD38-NAD 轴在影响染色质重塑和重新布线 T 细胞反应中的关键作用。总的来说，本综述强调了 CD38-NAD 轴在改变各种病理生理条件下 T 细胞反应中的重要贡献。
