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Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery

Author

Listed:
  • Minako Ito

    (Keio University School of Medicine)

  • Kyoko Komai

    (Keio University School of Medicine)

  • Setsuko Mise-Omata

    (Keio University School of Medicine)

  • Mana Iizuka-Koga

    (Keio University School of Medicine)

  • Yoshiko Noguchi

    (Keio University School of Medicine)

  • Taisuke Kondo

    (Keio University School of Medicine)

  • Ryota Sakai

    (Keio University School of Medicine)

  • Kazuhiko Matsuo

    (Kindai University Faculty of Pharmacy)

  • Takashi Nakayama

    (Kindai University Faculty of Pharmacy)

  • Osamu Yoshie

    (The Health and Kampo Institute)

  • Hiroko Nakatsukasa

    (Keio University School of Medicine)

  • Shunsuke Chikuma

    (Keio University School of Medicine)

  • Takashi Shichita

    (Keio University School of Medicine
    Stroke Renaissance Project, Tokyo Metropolitan Institute of Medical Science)

  • Akihiko Yoshimura

    (Keio University School of Medicine)

Abstract

In addition to maintaining immune tolerance, FOXP3+ regulatory T (Treg) cells perform specialized functions in tissue homeostasis and remodelling1,2. However, the characteristics and functions of brain Treg cells are not well understood because there is a low number of Treg cells in the brain under normal conditions. Here we show that there is massive accumulation of Treg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain Treg cells are similar to Treg cells in other tissues such as visceral adipose tissue and muscle3–5, they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT7. The amplification of brain Treg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain Treg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that Treg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.

Suggested Citation

  • Minako Ito & Kyoko Komai & Setsuko Mise-Omata & Mana Iizuka-Koga & Yoshiko Noguchi & Taisuke Kondo & Ryota Sakai & Kazuhiko Matsuo & Takashi Nakayama & Osamu Yoshie & Hiroko Nakatsukasa & Shunsuke Chi, 2019. "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery," Nature, Nature, vol. 565(7738), pages 246-250, January.
    • Handle: RePEc:nat:nature:v:565:y:2019:i:7738:d:10.1038_s41586-018-0824-5
    DOI: 10.1038/s41586-018-0824-5
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    Citations

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    Cited by:

    1. Jin Liu & Lihong Pan & Wenxuan Hong & Siqin Chen & Peiyuan Bai & Wei Luo & Xiaolei Sun & Furong He & Xinlin Jia & Jialiang Cai & Yingjie Chen & Kai Hu & Zhenju Song & Junbo Ge & Aijun Sun, 2022. "GPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Mark Walkenhorst & Jana K. Sonner & Nina Meurs & Jan Broder Engler & Simone Bauer & Ingo Winschel & Marcel S. Woo & Lukas Raich & Iris Winkler & Vanessa Vieira & Lisa Unger & Gabriela Salinas & Olivie, 2024. "Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Rhonda L. McFleder & Anastasiia Makhotkina & Janos Groh & Ursula Keber & Fabian Imdahl & Josefina Peña Mosca & Alina Peteranderl & Jingjing Wu & Sawako Tabuchi & Jan Hoffmann & Ann-Kathrin Karl & Axel, 2023. "Brain-to-gut trafficking of alpha-synuclein by CD11c+ cells in a mouse model of Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Stefano Suzzi & Tommaso Croese & Adi Ravid & Or Gold & Abbe R. Clark & Sedi Medina & Daniel Kitsberg & Miriam Adam & Katherine A. Vernon & Eva Kohnert & Inbar Shapira & Sergey Malitsky & Maxim Itkin &, 2023. "N-acetylneuraminic acid links immune exhaustion and accelerated memory deficit in diet-induced obese Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Bhavana Nayer & Jean L. Tan & Yasmin K. Alshoubaki & Yen-Zhen Lu & Julien M. D. Legrand & Sinnee Lau & Nan Hu & Anthony J. Park & Xiao-Nong Wang & Daniela Amann-Zalcenstein & Peter F. Hickey & Trevor , 2024. "Local administration of regulatory T cells promotes tissue healing," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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