Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma

Cugurra, Andrea; Mamuladze, Tornike; Rustenhoven, Justin; Dykstra, Taitea; Beroshvili, Giorgi; Greenberg, Zev J.; Baker, Wendy; Papadopoulos, Zachary; Drieu, Antoine; Blackburn, Susan M.; Kanamori, Mitsuhiro; Brioschi, Simone; Herz, Jasmin; Schuettpelz, Laura G.; Colonna, Marco; Smirnov, Igor; Kipnis, Jonathan

doi:10.1126/science.abf7844

Cited by 320 publications

(290 citation statements)

References 46 publications

(58 reference statements)

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“…Another important difference is that leptomeningeal BAMS are long-lived while dural BAMs are continuously renewed by peripheral monocytes ( Goldmann et al, 2016 ; Van Hove et al, 2019 ). The bone marrow in the calvarium and vertebral column specifically supply monocytes and neutrophils to the dura during homeostasis ( Cugurra et al, 2021 ) and to the meninges and brain parenchyma following brain injury or in neuroinflammation via vascular tunnels connecting the bone marrow and dura ( Herisson et al, 2018 ; Cai et al, 2019 ; Cugurra et al, 2021 ). The unique properties seen among leptomeningeal and dural BAMs is consistent with specialized functions for these populations in their respective barrier and non-barrier compartments.…”

Section: Meningeal Cell Typesmentioning

confidence: 99%

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Derk

Jones

Como

et al. 2021

Front. Cell. Neurosci.

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The meninges are the fibrous covering of the central nervous system (CNS) which contain vastly heterogeneous cell types within its three layers (dura, arachnoid, and pia). The dural compartment of the meninges, closest to the skull, is predominantly composed of fibroblasts, but also includes fenestrated blood vasculature, an elaborate lymphatic system, as well as immune cells which are distinct from the CNS. Segregating the outer and inner meningeal compartments is the epithelial-like arachnoid barrier cells, connected by tight and adherens junctions, which regulate the movement of pathogens, molecules, and cells into and out of the cerebral spinal fluid (CSF) and brain parenchyma. Most proximate to the brain is the collagen and basement membrane-rich pia matter that abuts the glial limitans and has recently be shown to have regional heterogeneity within the developing mouse brain. While the meninges were historically seen as a purely structural support for the CNS and protection from trauma, the emerging view of the meninges is as an essential interface between the CNS and the periphery, critical to brain development, required for brain homeostasis, and involved in a variety of diseases. In this review, we will summarize what is known regarding the development, specification, and maturation of the meninges during homeostatic conditions and discuss the rapidly emerging evidence that specific meningeal cell compartments play differential and important roles in the pathophysiology of a myriad of diseases including: multiple sclerosis, dementia, stroke, viral/bacterial meningitis, traumatic brain injury, and cancer. We will conclude with a list of major questions and mechanisms that remain unknown, the study of which represent new, future directions for the field of meninges biology.

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Section: Meningeal Cell Typesmentioning

confidence: 99%

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Derk

Jones

Como

et al. 2021

Front. Cell. Neurosci.

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“…Given the salient role of microglia in AD pathogenesis, these findings suggest that the skull bone marrow serves as an important source of peripherally-derived monocytes and microglia that contribute to the disease process (70). Additionally, it has recently been reported that the majority of myeloid cells in the meninges are derived from the skull bone marrow both in homeostatic and pathological states (72). Of note as well is the role of the skull bone marrow as a source of B cells to the meninges, with these developing B cells travelling via the direct vascular network to the meninges to complete their maturation (73).…”

Section: Meninges Choroid Plexus and Skull Bone Marrowmentioning

confidence: 99%

The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Chee

Solito

2021

Front. Immunol.

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease strongly associated with increasing age. Neuroinflammation and the accumulation of amyloid protein are amongst the hallmarks of this disease and most translational research to date has focused on targeting these two processes. However, the exact etiology of AD remains to be fully elucidated. When compared alongside, the immune response in AD closely resembles the central nervous system (CNS) immune changes seen in elderly individuals. It is possible that AD is a pathological consequence of an aged immune system secondary to chronic stimulation by a previous or ongoing insult. Pathological changes like amyloid accumulation and neuronal cell death may reflect this process of immunosenescence as the CNS immune system fails to maintain homeostasis in the CNS. It is likely that future treatments designed to modulate the aged immune system may prove beneficial in altering the disease course. The development of new tests for appropriate biomarkers would also be essential in screening for patients most likely to benefit from such treatments.

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“…A chemokine analysis from the Ivy Atlas suggests differential expression of immune populations at the infiltrating edge [38]. The CNS borders are populated by myeloid cells from adjacent bone-marrow niches that supply innate immune cells under homeostatic and pathological conditions [39]. Additionally, there appears to be a predilection of T cells in the perivascular tumor regions [40].…”

Section: Immune Landscape Distributionmentioning

confidence: 99%

Immune Microenvironment Landscape in CNS Tumors and Role in Responses to Immunotherapy

Najem

Khasraw

Heimberger

2021

Cells

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Despite the important evolution of immunotherapeutic agents, brain tumors remain, in general, refractory to immune therapeutics. Recent discoveries have revealed that the glioma microenvironment includes a wide variety of immune cells in various states that play an important role in the process of tumorigenesis. Anti-tumor immune activity may be occurring or induced in immunogenic hot spots or at the invasive edge of central nervous system (CNS) tumors. Understanding the complex heterogeneity of the immune microenvironment in gliomas will likely be the key to unlocking the full potential of immunotherapeutic strategies. An essential consideration will be the induction of immunological effector responses in the setting of the numerous aspects of immunosuppression and evasion. As such, immune therapeutic combinations are a fundamental objective for clinical studies in gliomas. Through immune profiling conducted on immune competent murine models of glioma and ex vivo human glioma tissue, we will discuss how the frequency, distribution of immune cells within the microenvironment, and immune modulatory processes, may be therapeutically modulated to lead to clinical benefits.

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Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma

Cited by 320 publications

References 46 publications

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease

The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Immune Microenvironment Landscape in CNS Tumors and Role in Responses to Immunotherapy

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