NAD + protects against EAE by regulating CD4 + T-cell differentiation

CD4 + T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD + ) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4 + IFNγ + IL-10 + T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD + regulates CD4 + T-cell differentiation through tryptophan hydroxylase-1 ( Tph1 ), independently of well-established transcription factors. In the presence of NAD + , the frequency of T-bet −/− CD4 + IFNγ + T cells was twofold higher than wild-type CD4 + T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4 + T-cell differentiation and demonstrate that NAD + may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases.