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 journalLetter

19 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

Fingerprint

Regulatory T-Lymphocytes
Brain
Stroke
Chemokine CCL1
Chemokine CCL20
Immune Tolerance
Intra-Abdominal Fat
T-Cell Antigen Receptor
Epidermal Growth Factor Receptor
Brain Injuries
Nervous System
Interleukin-2
Serotonin
Homeostasis
Rehabilitation
Ligands

ASJC Scopus subject areas

  • General

Cite this

Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. / Ito, Minako; Komai, Kyoko; Mise-Omata, Setsuko; Iizuka-Koga, Mana; Noguchi, Yoshiko; Kondo, Taisuke; Sakai, Ryota; Matsuo, Kazuhiko; Nakayama, Takashi; Yoshie, Osamu; Nakatsukasa, Hiroko; Chikuma, Shunsuke; Shichita, Takashi; Yoshimura, Akihiko.

In: Nature, Vol. 565, No. 7738, 10.01.2019, p. 246-250.

Research output: Contribution to journalLetter

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, vol. 565, no. 7738, pp. 246-250. https://doi.org/10.1038/s41586-018-0824-5
Ito M, Komai K, Mise-Omata S, Iizuka-Koga M, Noguchi Y, Kondo T et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature. 2019 Jan 10;565(7738):246-250. https://doi.org/10.1038/s41586-018-0824-5
Ito, Minako ; Komai, Kyoko ; Mise-Omata, Setsuko ; Iizuka-Koga, Mana ; Noguchi, Yoshiko ; Kondo, Taisuke ; Sakai, Ryota ; Matsuo, Kazuhiko ; Nakayama, Takashi ; Yoshie, Osamu ; Nakatsukasa, Hiroko ; Chikuma, Shunsuke ; Shichita, Takashi ; Yoshimura, Akihiko. / Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. In: Nature. 2019 ; Vol. 565, No. 7738. pp. 246-250.
@article{33b9ebc26b5d43c881cb5874bde28a13,
title = "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery",
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.",
author = "Minako Ito and Kyoko Komai and Setsuko Mise-Omata and Mana Iizuka-Koga and Yoshiko Noguchi and Taisuke Kondo and Ryota Sakai and Kazuhiko Matsuo and Takashi Nakayama and Osamu Yoshie and Hiroko Nakatsukasa and Shunsuke Chikuma and Takashi Shichita and Akihiko Yoshimura",
year = "2019",
month = "1",
day = "10",
doi = "10.1038/s41586-018-0824-5",
language = "English",
volume = "565",
pages = "246--250",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7738",

}

TY - JOUR

T1 - Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery

AU - Ito, Minako

AU - Komai, Kyoko

AU - Mise-Omata, Setsuko

AU - Iizuka-Koga, Mana

AU - Noguchi, Yoshiko

AU - Kondo, Taisuke

AU - Sakai, Ryota

AU - Matsuo, Kazuhiko

AU - Nakayama, Takashi

AU - Yoshie, Osamu

AU - Nakatsukasa, Hiroko

AU - Chikuma, Shunsuke

AU - Shichita, Takashi

AU - Yoshimura, Akihiko

PY - 2019/1/10

Y1 - 2019/1/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85059751491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059751491&partnerID=8YFLogxK

U2 - 10.1038/s41586-018-0824-5

DO - 10.1038/s41586-018-0824-5

M3 - Letter

VL - 565

SP - 246

EP - 250

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 7738

ER -