CD38: T Cell Immuno-Metabolic Modulator.

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.