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-HT₇. 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.