The meninges host a unique compartment of regulatory T cells that bulwarks adult hippocampal neurogenesis [scRNA-Seq]

Our knowledge about the meningeal immune system has recently burgeoned, particularly how innate and adaptive effector cells are mobilized in response to brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains sparse. This study highlights the heterogeneous and polyfunctional regulatory T (Treg) cell compartment in mouse meninges. A Treg subtype specialized in controlling Th1-cell responses and another subtype devoted to controlling responses in B-cell follicles were substantial components of this compartment, foretelling the finding that punctual Treg-cell ablation rapidly unleashed interferon-gamma production by meningeal lymphocytes, unlocked their access to the brain parenchyma, and altered meningeal B-cell profiles. Distally, the hippocampus took on a reactive state, with activation of multiple glial-cell types; within the dentate gyrus, neural stem cells showed exacerbated death and desisted from further differentiation, associated with inhibition of spatial-reference memory. Thus, meningeal Treg cells are a multifaceted bulwark to brain homeostasis at steady-state.