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

Nature communications (2014-10-08)
Stefan G Tullius, Hector Rodriguez Cetina Biefer, Suyan Li, Alexander J Trachtenberg, Karoline Edtinger, Markus Quante, Felix Krenzien, Hirofumi Uehara, Xiaoyong Yang, Haydn T Kissick, Winston P Kuo, Ionita Ghiran, Miguel A de la Fuente, Mohamed S Arredouani, Virginia Camacho, John C Tigges, Vasilis Toxavidis, Rachid El Fatimy, Brian D Smith, Anju Vasudevan, Abdallah ElKhal
RESUMEN

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.

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