Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery
Abstract
In addition to maintaining immune tolerance, FOXP3 + regulatory T (T reg ) cells perform specialized functions in tissue homeostasis and remodelling 1,2 . However, the characteristics and functions of brain T reg cells are not well understood because there is a low number of T reg cells in the brain under normal conditions. Here we show that there is massive accumulation of T reg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain T reg cells are similar to T reg cells in other tissues such as visceral adipose tissue and muscle 3-5 , they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT 7 . The amplification of brain T reg 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 T reg 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 T reg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.
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Treg cell-derived amphiregulin (Areg) promotes repair after acute tissue injury.
“Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair after acute tissue injury.”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [27]
Treg cells protect from epithelial cell injury by both interacting with immune cells to suppress inflammation and by producing epithelial growth factors that signal to non-immune cells.
“Together, these studies suggest that Treg cells protect from epithelial cell injury by both interacting with immune cells to suppress inflammation and by producing epithelial growth factors that signal to non-immune cells.”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [27]
TCR signaling is thought to contribute to Treg cell accumulation in the brain and VAT.
“As TCR signaling is thought to contribute to Treg cell accumulation in the brain and VAT 27,35”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [27]
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- Authors
- 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.
- Affiliations
- Keio University (JP)
- Kindai University (JP)
- Corresponding author
- Ito, Minako
- Yoshimura, Akihiko
- ORCID
- Venue
- Nature
- Published
- 2019-01
- Volume
- 565
- Issue
- 7738
- Pages
- 246-250
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2906480617
- Cited by
- 784
- References
- 6
- Citations by year
- 2026: 72 · 2025: 125 · 2024: 121 · 2023: 112 · 2022: 116 · 2021: 120 · 2020: 72 · 2019: 45
- FWCI
- 26.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (20K20384, 16K09867, 17K19571, 18K15129, 17H06175, 17H05096)
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Foxp3, ischemic stroke, astrocyte activation, neurological recovery, amphiregulin, 5-HT7 receptor, interleukin-2, IL-33, CCL1, CCL20, neuroinflammation, epidermal growth factor receptor ligands, neuroprotection
- MeSH terms
- Neuroprotection, Interleukin-33, Animals, Astrocytes, Brain, Cell Movement, Brain Ischemia, Gliosis, Interleukin-2, Male, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Receptors, Serotonin, Serotonin, Signal Transduction, Interleukin-6, Cell Proliferation, T-Lymphocytes, Regulatory, STAT3 Transcription Factor, Mice, Receptors, CCR, Chemokine CCL1, Chemokine CCL20
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