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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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Citations
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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.
Journal ArticleDOI

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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Journal ArticleDOI

RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation

TL;DR: It is reported that interleukin 23 and the transcription factor RORγt drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-γ (IFN-γ) and IL-27 acted as negative regulators.
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Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling

TL;DR: It is shown that interleukin-1 (IL-1) signaling on T cells is critically required for the early programming of Th 17 cell lineage and Th17 cell-mediated autoimmunity and this pathway may serve as a unique target for Th17cell-mediated immunopathology.
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Targeting IL-17 and TH17 cells in chronic inflammation.

TL;DR: This Review focuses on the current knowledge of the IL-17–TH17 cell pathway to better understand the positive as well as potential negative consequences of targeting them.
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Fate mapping of IL-17-producing T cells in inflammatory responses

TL;DR: A reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A) allows the actual functional fate of effector T cells to be related to TH17 developmental origin regardless of IL-17 expression.
Journal ArticleDOI

Three or more routes for leukocyte migration into the central nervous system

TL;DR: This review discusses three distinct routes for leukocyte entry into the central nervous system and considers how different populations of leukocytes use trafficking signals to gain entry.
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