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 CD38(−)NAD(+) axis in altering T cell response in various pathophysiological conditions.