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Cytokine networks in neuroinflammation

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TLDR
Recent observations on the impact of dysregulated cytokine networks in neuroinflammation are summarized.
Abstract
Cytokines provide cells with the ability to communicate with one another and orchestrate complex multicellular behaviour. There is an emerging understanding of the role that cytokines play in normal homeostatic tissue function and how dysregulation of these cytokine networks is associated with pathological conditions. The central nervous system (CNS), where few blood-borne immune cells circulate, seems to be particularly vulnerable to dysregulated cytokine networks. In degenerative diseases, such as proteopathies, CNS-resident cells are the predominant producers of pro-inflammatory cytokines. By contrast, in classical neuroinflammatory diseases, such as multiple sclerosis and encephalitides, pro-inflammatory cytokines are mainly produced by tissue-invading leukocytes. Whereas the effect of dysregulated cytokine networks in proteopathies is controversial, cytokines delivered to the CNS by invading immune cells are in general detrimental to the tissue. Here, we summarize recent observations on the impact of dysregulated cytokine networks in neuroinflammation.

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High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease

TL;DR: High‐dimensional cytometry reveals that microglia, several subsets of border‐associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease‐specific transformations in the immune microenvironment during aging and in models of Alzheimer’s disease and multiple sclerosis.
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An Inflammation-Centric View of Neurological Disease: Beyond the Neuron.

TL;DR: This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia- glia interactions, then conclude with a consideration of how a cell's endogenous mechanisms might be leveraged to provide a therapeutic strategy to target neuro inflammation.
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The Meningeal Lymphatic System: A New Player in Neurophysiology.

TL;DR: The meningeal lymphatic system can be viewed as a novel player in neurophysiology by altering the accessibility of CSF-borne immune neuromodulators to the brain parenchyma, thereby altering their effects on the brain.
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Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis

TL;DR: A single-cell characterization of cerebrospinal fluid and blood of newly diagnosed multiple sclerosis patients is provided, revealing altered composition of lymphocyte and monocyte subsets, validated by other methods including the interrogation of the TFH subset in mouse models of MS.
References
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Granulocyte Macrophage Colony-Stimulating Factor A New Putative Therapeutic Target in Multiple Sclerosis

TL;DR: Key activities for GM-CSF are revealed in the development of inflammatory demyelinating lesions and control of migration and/or proliferation of leukocytes within the CNS, which hold implications for the pathogenesis of inflammatory and demYelinating diseases.
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Stroma-Derived Interleukin-34 Controls the Development and Maintenance of Langerhans Cells and the Maintenance of Microglia

TL;DR: It is shown that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain.
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What is the blood–brain barrier (not)?

TL;DR: The BBB is re-define as a capillary barrier for solutes, and it is clarified that leukocyte recruitment requires two differentially regulated steps: passage across postcapillary venules into Virchow-Robin spaces, and subsequent progression across the glia limitans into the neuropil.
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Therapeutic opportunities of the IL-22-IL-22R1 system.

TL;DR: Current knowledge of the biology of the IL-22–IL-22R1 system, its role in inflammation, tissue protection, regeneration and antimicrobial defence, as well as the positive and potentially negative consequences of its therapeutic modulation are highlighted.
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