Adaptive immune responses in the skull bone marrow for CNS immunosurveillance and brain tumor immunity 2247790

Abstract Introduction Mounting evidence indicates that the central nervous system (CNS) maintains active communication with the peripheral immune system, yet the mechanisms by which adaptive immunity monitors the CNS remain incompletely understood. Recent discoveries have revealed specialized vascular and cellular conduits linking the dura mater with the skull, allowing cerebrospinal fluid and immune cell exchange between the CNS and the skull bone marrow (BM) under both steady-state and pathological conditions. Although the skull BM has been recognized as a reservoir of innate immune cells supporting CNS immunity, its contribution to adaptive immune responses has not been thoroughly defined. Methods We analyzed mouse skull bone marrow using single-cell RNA sequencing, flow cytometry, and confocal imaging. Results In this study, we describe organized lymphoid aggregates within the skull BM that display germinal center-like architecture and contain a distinct subset of follicular helper T cells. These T cells drive B cell activation and humoral responses through their communications. We show that adaptive immune cells within these skull BM niches detect and react to CNS-derived antigens and are indispensable for effective antitumor immunity in mouse models of brain cancer. Conclusion Our identification of these specialized adaptive immune hubs in the skull BM establishes a new paradigm for CNS immunosurveillance and unveils therapeutic opportunities for neurological disorders, including malignancies of the brain. Funding Source The ChadTough Foundation Topic Categories Neuroimmunology (NEUR)