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

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 and Abdallah ElKhal ()
Additional contact information
Stefan G. Tullius: Brigham and Women’s Hospital, Harvard Medical School
Hector Rodriguez Cetina Biefer: Brigham and Women’s Hospital, Harvard Medical School
Suyan Li: Angiogenesis and Brain Development Laboratory, McLean Hospital/Harvard Medical School
Alexander J. Trachtenberg: Harvard Catalyst-Laboratory for Innovative Translational Technologies, Harvard Medical School
Karoline Edtinger: Brigham and Women’s Hospital, Harvard Medical School
Markus Quante: Brigham and Women’s Hospital, Harvard Medical School
Felix Krenzien: Brigham and Women’s Hospital, Harvard Medical School
Hirofumi Uehara: Brigham and Women’s Hospital, Harvard Medical School
Xiaoyong Yang: Brigham and Women’s Hospital, Harvard Medical School
Haydn T. Kissick: Beth Israel Deaconess Medical Center, Harvard Medical School
Winston P. Kuo: Harvard Catalyst-Laboratory for Innovative Translational Technologies, Harvard Medical School
Ionita Ghiran: Beth Israel Deaconess Medical Center, Harvard Medical School
Miguel A. de la Fuente: Instituto de Biología y Genética Molecular, University of Valladolid
Mohamed S. Arredouani: Beth Israel Deaconess Medical Center, Harvard Medical School
Virginia Camacho: Flow Cytometry Core Facility, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute
John C. Tigges: Flow Cytometry Core Facility, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute
Vasilis Toxavidis: Flow Cytometry Core Facility, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute
Rachid El Fatimy: Center for Neurological Diseases, Brigham and Women’s Hospital, Harvard Medical School
Brian D. Smith: Transplantation Research Center, Brigham and Women's Hospital and Children's Hospital, Harvard Medical School
Anju Vasudevan: Angiogenesis and Brain Development Laboratory, McLean Hospital/Harvard Medical School
Abdallah ElKhal: Brigham and Women’s Hospital, Harvard Medical School

Nature Communications, 2014, vol. 5, issue 1, 1-17

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6101

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