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

Author

Listed:
  • Stefan G. Tullius

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Hector Rodriguez Cetina Biefer

    (Brigham and Women’s Hospital, Harvard Medical School
    Clinic for Cardiovascular Surgery, University Hospital Zurich)

  • 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)

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.

Suggested Citation

  • 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 & Wi, 2014. "NAD+ protects against EAE by regulating CD4+ T-cell differentiation," Nature Communications, Nature, vol. 5(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6101
    DOI: 10.1038/ncomms6101
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    Cited by:

    1. Xiao-Ru Ma & Xudong Zhu & Yujie Xiao & Hui-Min Gu & Shuang-Shuang Zheng & Liang Li & Fan Wang & Zhao-Jun Dong & Di-Xian Wang & Yang Wu & Chenyu Yang & Wenhong Jiang & Ke Yao & Yue Yin & Yang Zhang & C, 2022. "Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Quetzalcoatl Escalante-Covarrubias & Lucía Mendoza-Viveros & Mirna González-Suárez & Román Sitten-Olea & Laura A. Velázquez-Villegas & Fernando Becerril-Pérez & Ignacio Pacheco-Bernal & Erick Carreño-, 2023. "Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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