Tullius, StefanBiefer, Hector Rodriguez CetinaLi, SuyanTrachtenberg, Alexander J.Edtinger, KarolineQuante, MarkusKrenzien, FelixUehara, HirofumiYang, XiaoyongKissick, Haydn T.Kuo, Winston P.Ghiran, Ionitade la Fuente, Miguel A.Arredouani, Mohamed SimoCamacho, VirginiaTigges, John C.Toxavidis, VasilisEl Fatimy, RachidSmith, Brian D.Vasudevan, AnjuElKhal, Abdallah2014-11-032014Tullius, S. G., H. R. C. Biefer, S. Li, A. J. Trachtenberg, K. Edtinger, M. Quante, F. Krenzien, et al. 2014. “NAD+ protects against EAE by regulating CD4+ T-cell differentiation.” Nature Communications 5 (1): 5101. doi:10.1038/ncomms6101. http://dx.doi.org/10.1038/ncomms6101.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347585CD4+ 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.en-USJournal Article2014-11-0310.1038/ncomms6101