Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery

Nature. 2019 Jan;565(7738):246-250. doi: 10.1038/s41586-018-0824-5. Epub 2019 Jan 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / pathology*
  • Brain / cytology
  • Brain / immunology
  • Brain Ischemia / immunology*
  • Brain Ischemia / pathology*
  • Cell Movement
  • Cell Proliferation
  • Chemokine CCL1 / immunology
  • Chemokine CCL20 / immunology
  • Gliosis / pathology*
  • Interleukin-2 / immunology
  • Interleukin-33 / immunology
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotection / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, CCR / metabolism
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Serotonin / metabolism
  • Signal Transduction
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • CCL20 protein, mouse
  • Ccl1 protein, mouse
  • Chemokine CCL1
  • Chemokine CCL20
  • Interleukin-2
  • Interleukin-33
  • Interleukin-6
  • Receptors, Antigen, T-Cell
  • Receptors, CCR
  • Receptors, Serotonin
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • serotonin 7 receptor
  • Serotonin