CNS-derived Tregs regulate peripheral immune responses 4272

Abstract Description The CNS is isolated from the periphery by barriers and is believed to lack immune responses. The lymphatic system links CNS peptides to the dura mater, where antigen-presenting cells activate T cells in the meninges. In this study, we aim to investigate whether CNS-derived peptides drive the generation of CNS-educated regulatory T cells (Tregs) in the brain borders. Using adoptive transfer systems, we demonstrate that CNS peptides promote naïve T cells’ differentiation into CNS-border-Treg cells. Injection of MHC-II neoantigen into the cerebrospinal fluid accelerates tumor growth by promoting tetramer-specific Tregs. Our data demonstrate that skull and vertebra bone marrows are richer in Tregs than peripheral counterparts, with quiescent markers distinguishing skull Tregs from activated dura mater Tregs. Shared Treg clones between meninges and adjacent bone marrow suggest skull Tregs migrate to the dura mater for activation. In CNS autoimmunity, Tregs from the skull reach the brain and spinal cord parenchyma. Thus, manipulating the CNS-tolerogenic environment could be therapeutic for peripheral immune response control. Funding Sources Supported by NIH/NIA AG034113, NMSS FG-2307-42179 Topic Categories Neuroimmunology (NEUR)