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Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [dura/skull/sternum]

ABSTRACT: Accumulating evidence demonstrates that the central nervous system (CNS) is not disconnected from the peripheral immune system; however, precisely how the adaptive immune system surveils the CNS remains a critical question. Recent findings reveal that channels between the dura mater and the skull facilitate the exchange of cerebrospinal fluid and immune cells between the CNS and skull bone marrow (BM) under both homeostatic and disease conditions. Skull BM serves as a source of innate immune cells for the CNS, yet its role in adaptive immune responses remains insufficiently characterized. Here, we identify lymphoid structures within the skull BM, featuring germinal center-like formations and harboring a distinct population of follicular helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21, and IFN-γ signaling. Adaptive immune cells within these skull BM lymphoid structures surveil and respond to CNS-derived antigens, which we demonstrate to be critical for optimal antitumor immunity in murine brain cancer models. Our discovery of distinct anatomical sites in the skull BM that enable adaptive immunosurveillance of the CNS highlights promising avenues for immunotherapies targeting neurological diseases, including brain cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE313969 | GEO | 2026/07/13

REPOSITORIES: GEO

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Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/sternum]

Project description:Accumulating evidence demonstrates that the central nervous system (CNS) is not disconnected from the peripheral immune system; however, precisely how the adaptive immune system surveils the CNS remains a critical question. Recent findings reveal that channels between the dura mater and the skull facilitate the exchange of cerebrospinal fluid and immune cells between the CNS and skull bone marrow (BM) under both homeostatic and disease conditions. Skull BM serves as a source of innate immune cells for the CNS, yet its role in adaptive immune responses remains insufficiently characterized. Here, we identify lymphoid structures within the skull BM, featuring germinal center-like formations and harboring a distinct population of follicular helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21, and IFN-γ signaling. Adaptive immune cells within these skull BM lymphoid structures surveil and respond to CNS-derived antigens, which we demonstrate to be critical for optimal antitumor immunity in murine brain cancer models. Our discovery of distinct anatomical sites in the skull BM that enable adaptive immunosurveillance of the CNS highlights promising avenues for immunotherapies targeting neurological diseases, including brain cancers.

2026-07-13 | GSE309634 | GEO

Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/brain]

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Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/sternum]

Project description:Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/sternum]

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Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/brain]

Project description:Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [skull/brain]

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Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [dura/skull/sternum]

Project description:Lymphoid structures in the skull bone marrow control homeostatic and anti-tumor immune responses in the CNS [dura/skull/sternum]

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Venous plexus-associated lymphoid hubs support meningeal humoral immunity

Project description:There is increasing interest in how immune cells in the meninges, the membranes that surround the brain and spinal cord, contribute to homeostasis and disease in the central nervous system (CNS)1,2. The outer layer of meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and function as a site for B cell development. Here, we identified organised lymphoid structures protecting fenestrated vasculature in the dura mater that we term dural-associated lymphoid tissue (DALT). We found the most elaborate immune organization, including lymphatic vessels, surrounding the rostral_x0002_rhinal confluence of sinuses. We termed this structure that interfaced with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or following challenge with systemic or nasal antigens. DALT contained germinal centre (GC) B cells, and supported the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate lymphoid architecture around vasculature in dura mater that can sample antigens and rapidly support humoral immune responses following local pathogen challenge.

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2025-12-01 | PXD058239 | Pride

Ependymoma instructs cranial haematopoiesis and immunotolerance

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