Brain regulatory T cells

The brain, long thought to be isolated from the peripheral immune system, is increasingly recognized to be integrated into a systemic immunological network. These conduits of immune–brain interaction and immunosurveillance processes necessitate the presence of complementary immunoregulatory mechanisms, of which brain regulatory T cells (T reg cells) are likely a key facet. T reg cells represent a dynamic population in the brain, with continual influx, specialization to a brain-residency phenotype and relatively rapid displacement by newly incoming cells. In addition to their functions in suppressing adaptive immunity, an emerging view is that T reg cells in the brain dampen down glial reactivity in response to a range of neurological insults, and directly assist in multiple regenerative and reparative processes during tissue pathology. The utility and malleability of the brain T reg cell population make it an attractive therapeutic target across the full spectrum of neurological conditions, ranging from neuroinflammatory to neurodegenerative and even psychiatric diseases. Therapeutic modalities currently under intense development include T reg cell therapy, IL-2 therapy to boost T reg cell numbers and multiple innovative approaches to couple these therapeutics to brain delivery mechanisms for enhanced potency. Here we review the state of the art of brain T reg cell knowledge together with the potential avenues for future integration into medical practice. In this Review, Liston et al. discuss the biology of regulatory T cells (T reg cells) in the brain. They consider how T reg cells are recruited to the brain and their anti-inflammatory and reparative functions in brain tissue. Finally, they highlight the potential for targeting brain T reg cells to treat a range of neurological diseases.