Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery.

In addition to maintaining immune tolerance, FOXP3 regulatory T (T) cells perform specialized functions in tissue homeostasis and remodelling. However, the characteristics and functions of brain T cells are not well understood because there is a low number of T cells in the brain under normal conditions. Here we show that there is massive accumulation of T cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain T cells are similar to T cells in other tissues such as visceral adipose tissue and muscle, they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT. The amplification of brain T 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 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 cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.