Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery

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 Chikuma, Takashi Shichita, Akihiko Yoshimura

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)246-250
Number of pages5
JournalNature
Volume565
Issue number7738
DOIs
Publication statusPublished - 2019 Jan 10

ASJC Scopus subject areas

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    Ito, M., Komai, K., Mise-Omata, S., Iizuka-Koga, M., Noguchi, Y., Kondo, T., Sakai, R., Matsuo, K., Nakayama, T., Yoshie, O., Nakatsukasa, H., Chikuma, S., Shichita, T., & Yoshimura, A. (2019). Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature, 565(7738), 246-250. https://doi.org/10.1038/s41586-018-0824-5