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. Overall design: We investigated the transcriptional heterogeneity of meningeal CD4+ T cells via single-cell RNA and Tcr sequencing (scRNA-seq/ scTcr-seq), and investigate the changes in the hippocampal niche after punctual Treg cell depletion via diphtheria toxin (DT) injections into Foxp3-DTR+ and littermate Foxp3-DTR- controls (scRNA-seq) .For standard genome-wide scRNA-seq analyses, non neuronal non microglia (Live CD45- Thy1-) were sorted by flow cytometry and encapsulated using the Chromium Single Cell 3' v2 platform. For coupled scRNA-seq and scTcr-seq, CD4+ T cells from meninges of Foxp3Gfp mice and b6 wildtype mice were sorted and encapsulated using the Chromium Single Cell 5' v3 and V(D)J platform (10x Genomics).