Inflammation and immune responses after stroke, including ischemic cerebral infarction, play pivotal roles in the pathology, resolution of inflammation, and neurological recovery. Regulatory T (Treg) cells are the cells responsible for immune tolerance, usually activated by secondary lymphatic tissues, which subsequently regulate effector T cell activation and dendritic cell activation. Recently, Tregs that are present in tissues, called tissue Tregs, have been shown to exhibit tissue-specific functions in addition to immune regulation, contributing to the maintenance of homeostasis and tissue repair. We found that Tregs accumulate in the brain at the chronic phase of ischemic brain injury and control astrogliosis through the secretion of amphiregulin. Unlike other tissue Tregs, brain Tregs express a serotonin receptor (Htr7) that is characteristic of the nervous system, and are proliferated and activated by serotonin. Administering a serotonin or selective serotonin reuptake inhibitor (SSRI) in an experimental stroke mouse model increased the number of brain Tregs and improved neurological symptoms. Elucidation of the significance of brain Tregs should also contribute to the understanding of other types of neuroinflammation.
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