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NADþ protects against EAE by regulating CD4þ T-cell differentiation Tullius, Stefan G. Rodriguez-Cetina Biefer, Héctor Li, Suyan Trachtenberg, Alexander J. Edtinger, Karoline Quante, Markus Krenzien, Felix Uehara, Hirofumi Yang, Xiaoyong Kissick, Haydn T. Kuo, Winston P. Ghiran, Ionita Fuente García, Miguel Ángel de la Arredouani, Mohamed S. Camacho, Virginia Tigges, John C. Toxavidis, Vasilis El Fatimy, Rachid Smith, Brian D. Vasudevan, Anju Elkhal, Abdallah Inmunología Medicamentos - Investigación Producción Científica 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. 2015-03-18T11:48:27Z 2015-03-18T11:48:27Z 2014 info:eu-repo/semantics/article Nature Communications, 2014, 5, Article number: 5101 2041-1723 http://uvadoc.uva.es/handle/10324/9465 10.1038/ncomms6101 Nature Communications 5 eng Attribution-NonCommercial-NoDerivatives 4.0 International info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Nature Publish Group https://uvadoc.uva.es/bitstream/10324/9465/6/1.%20M.A.%20de%20la%20FUENTE%20PD-216.pdf.jpg Hispana TEXT http://creativecommons.org/licenses/by-nc-nd/4.0/ UVaDOC. Repositorio Documental de la Universidad de Valladolid http://uvadoc.uva.es/handle/10324/9465