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Venous-plexus-associated lymphoid hubs support meningeal humoral immunity
Dural-associated lymphoid tissues are lymphoid structures around vascular hubs in the dura mater that sample antigens and rapidly support humoral immune responses after local pathogen challenge.
- Zachary Fitzpatrick
- , Nagela Ghabdan Zanluqui
- & Dorian B. McGavern
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Disease-associated astrocyte epigenetic memory promotes CNS pathology
In an experimental autoimmune encephalomyelitis model in mice, a subset of astrocytes retains an epigenetically regulated memory of past inflammation, causing exacerbated inflammation upon subsequent rechallenge.
- Hong-Gyun Lee
- , Joseph M. Rone
- & Francisco J. Quintana
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Article
| Open AccessMitochondrial complex I activity in microglia sustains neuroinflammation
Blocking mitochondrial complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in vivo in an animal disease model.
- L. Peruzzotti-Jametti
- , C. M. Willis
- & S. Pluchino
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| Open AccessAPOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.
- Michael S. Haney
- , Róbert Pálovics
- & Tony Wyss-Coray
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Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance
Rhythmic neural activity drives cerebrospinal fluid perfusion through brain parenchyma to enhance brain cleansing.
- Li-Feng Jiang-Xie
- , Antoine Drieu
- & Jonathan Kipnis
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| Open AccessB cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4
The immune system is tolerized against the neuromyelitis optica autoantigen AQP4 by thymic B cells, which present their endogenous AQP4 to AQP4-reactive thymocytes.
- Ali Maisam Afzali
- , Lucy Nirschl
- & Thomas Korn
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Identification of direct connections between the dura and the brain
Arachnoid cuff exit points create openings in the arachnoid barrier enabling the drainage of cerebrospinal fluid and exchange of molecules and cells between the dura and the subarachnoid space, therefore physically connecting the brain and the dura.
- Leon C. D. Smyth
- , Di Xu
- & Jonathan Kipnis
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| Open AccessCirculating myeloid-derived MMP8 in stress susceptibility and depression
Serum MMP8 is increased in stress-susceptible mice following chronic stress and leads to brain structure and behavioural changes in mice.
- Flurin Cathomas
- , Hsiao-Yun Lin
- & Scott J. Russo
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| Open AccessAutoreactive T cells target peripheral nerves in Guillain–Barré syndrome
Autoreactive T cells that target myelin antigens in the peripheral nerves are present in patients with the demyelinating form of Guillain–Barré syndrome, and these T cells are likely to contribute to disease pathophysiology.
- L. Súkeníková
- , A. Mallone
- & D. Latorre
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The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Stress-associated catecholamines promote CD8+ T cell exhaustion through the β1-adrenergic receptor, and blocking β-adrenergic signalling may help restore anti-tumour functions.
- Anna-Maria Globig
- , Steven Zhao
- & Susan M. Kaech
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Article
| Open AccessPlatelet factors attenuate inflammation and rescue cognition in ageing
Platelet factors transfer the benefits of young blood to the ageing brain in mice through CXCR3, which mediates the cellular, molecular and cognitive benefits of systemic PF4 on the aged brain.
- Adam B. Schroer
- , Patrick B. Ventura
- & Saul A. Villeda
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Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells
Lactate produced by dendritic cells (DCs) suppresses T-cell-mediated autoimmunity through a mechanism in which lactate activates HIF-1α–NDUFA4L2 signalling in DCs and thereby limits DC-mediated pro-inflammatory responses such as the development of encephalitogenic T cells.
- Liliana M. Sanmarco
- , Joseph M. Rone
- & Francisco J. Quintana
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| Open AccessMast cells link immune sensing to antigen-avoidance behaviour
Mast cells are shown to function as sensor cells linking antigen recognition in type 2 immunity to antigen-specific avoidance behaviour, preventing immune activation and inflammation.
- Thomas Plum
- , Rebecca Binzberger
- & Hans-Reimer Rodewald
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Locus for severity implicates CNS resilience in progression of multiple sclerosis
A genome-wide association study including 22,389 cases of multiple sclerosis finds an association with disease progression at the DYSF–ZNF638 and DNM3–PIGC loci and identifies a potential of higher educational attainment in slowing disease progression.
- Adil Harroud
- , Pernilla Stridh
- & Kári Stefánsson
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Dedicated macrophages organize and maintain the enteric nervous system
Resident macrophages of the muscularis externa refine the enteric nervous system (ENS) early in life by pruning synapses and phagocytosing enteric neurons, and later switch to a neuro-supportive function, indicating that the ENS is governed by a dedicated population of resident macrophages that adapt to the timely needs of the ENS.
- Maria Francesca Viola
- , Marta Chavero-Pieres
- & Guy Boeckxstaens
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| Open AccessAn airway-to-brain sensory pathway mediates influenza-induced sickness
A small population of prostaglandin E2-responsive glossopharyngeal sensory neurons provides a sensory pathway between airway and brainstem that mediates sickness responses to early-phase influenza virus infection.
- Na-Ryum Bin
- , Sara L. Prescott
- & Stephen D. Liberles
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Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion
Two Streptococcus spp. can utilize a neuropeptide (CGRP) and its receptor (RAMP1) on macrophages to promote brain invasion, a finding that may help the development of therapies for bacterial meningitis.
- Felipe A. Pinho-Ribeiro
- , Liwen Deng
- & Isaac M. Chiu
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Identification of astrocyte regulators by nucleic acid cytometry
The pathogenic function of XBP1-expressing astrocytes in experimental autoimmune encephalomyelitis and multiple sclerosis have been studied using FIND-seq, a new method combining microfluidics cytometry, PCR-based detection of nucleic acids and cell sorting for in-depth single-cell transcriptomics analyses of rare cells.
- Iain C. Clark
- , Michael A. Wheeler
- & Adam R. Abate
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Review Article |
Brain borders at the central stage of neuroimmunology
Anatomical, cellular and molecular immune interactions at the borders of the central nervous system control homeostatic brain function and can lead to neurological or psychiatric diseases, representing potential therapeutic targets.
- Justin Rustenhoven
- & Jonathan Kipnis
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Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid
Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.
- Antoine Drieu
- , Siling Du
- & Jonathan Kipnis
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| Open AccessNociceptor neurons affect cancer immunosurveillance
Melanoma cells interact with pain-mediating sensory neurons by increasing their release of the neuropeptide CGRP, which increases the exhaustion of CD8+ T cells and thus promotes the survival of cancer cells.
- Mohammad Balood
- , Maryam Ahmadi
- & Sebastien Talbot
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Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces
The development of a new genetic tool to selectively deplete or modify group 2 innate lymphoid cells (ILC2s) addresses the debate regarding the non-redundant functions of this immune cell type.
- Amy M. Tsou
- , Hiroshi Yano
- & David Artis
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Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry
Aberrantly formed microglia due to an adverse prenatal environment affect long-term microglia reactivity and proper striatal circuit development in mice
- Lindsay N. Hayes
- , Kyongman An
- & Akira Sawa
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| Open AccessBrainstem ADCYAP1+ neurons control multiple aspects of sickness behaviour
A studying using a set of unbiased methodologies shows that a specific subpopulation of neurons in the brainstem can regulate the diverse responses to a bacterial endotoxin that induces sickness behaviours.
- Anoj Ilanges
- , Rani Shiao
- & Jeffrey M. Friedman
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Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4
An immune signature characterized by activated antigen-specific CD8 T cells is identified in the brain and blood of mice with amyotrophic lateral sclerosis-4 (ALS4), suggesting that the immune system is involved in ALS4 neurodegeneration.
- Laura Campisi
- , Shahab Chizari
- & Ivan Marazzi
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A preoptic neuronal population controls fever and appetite during sickness
A newly identified population of neurons in the ventral medial preoptic area of the hypothalamus regulate stereotypical symptoms of illness, including fever and appetite suppression.
- Jessica A. Osterhout
- , Vikrant Kapoor
- & Catherine Dulac
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Brain motor and fear circuits regulate leukocytes during acute stress
Distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, calibrating the ability of the immune system to respond to physical threats.
- Wolfram C. Poller
- , Jeffrey Downey
- & Filip K. Swirski
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Specification of CNS macrophage subsets occurs postnatally in defined niches
Single-cell profiling and fate-mapping experiments in the developing brain of mice and humans show that microglia and meningeal macrophages originate from a common prenatal precursor, but that perivascular macrophages are derived postnatally from meningeal macrophages.
- Takahiro Masuda
- , Lukas Amann
- & Marco Prinz
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The lung microbiome regulates brain autoimmunity
Work in experimental autoimmune models shows that the lung microbiome is linked to immune reactivity in the brain through a mechanism in which the balance of pulmonary microorganisms regulates the activation state of microglia.
- Leon Hosang
- , Roger Cugota Canals
- & Francesca Odoardi
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Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.
- Tobias V. Lanz
- , R. Camille Brewer
- & William H. Robinson
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Exercise plasma boosts memory and dampens brain inflammation via clusterin
Plasma from voluntarily running mice reduces baseline expression of neuroinflammatory genes and experimentally induced brain inflammation when infused into sedentary mice.
- Zurine De Miguel
- , Nathalie Khoury
- & Tony Wyss-Coray
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Antigen-presenting innate lymphoid cells orchestrate neuroinflammation
A subset of inflammatory group 3 innate lymphoid cells, here termed iILC3s, infiltrate the central nervous system and promote neuroinflammation and disease progression in a mouse model of multiple sclerosis.
- John B. Grigg
- , Arthi Shanmugavadivu
- & Gregory F. Sonnenberg
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A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis
Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.
- Martina Absinta
- , Dragan Maric
- & Daniel S. Reich
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Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit
Signals from the sympathetic nervous system act via mesenchymal stromal cells to regulate the function of group 2 innate lymphoid cells and control adipocyte metabolism.
- Filipa Cardoso
- , Roel G. J. Klein Wolterink
- & Henrique Veiga-Fernandes
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Tonic prime-boost of STING signalling mediates Niemann–Pick disease type C
The lysosomal protein Niemann–Pick type C1 (NPC1) is identified as a cofactor in the trafficking of STING, and loss of NPC1 is shown to both ‘prime’ and ‘boost’ STING signalling leading to neurological disease.
- Ting-Ting Chu
- , Xintao Tu
- & Nan Yan
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Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
Interleukin-3 signalling from astrocytes to microglia readies microglia to defend against Alzheimer’s disease.
- Cameron S. McAlpine
- , Joseph Park
- & Filip K. Swirski
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Dysregulation of brain and choroid plexus cell types in severe COVID-19
Single-nucleus transcriptomes of frontal cortex and choroid plexus samples from patients with COVID-19 reveal pathological cell states that are similar to those associated with human neurodegenerative diseases and chronic brain disorders.
- Andrew C. Yang
- , Fabian Kern
- & Tony Wyss-Coray
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Sensory neuron-derived TAFA4 promotes macrophage tissue repair functions
Specialized somatosensory neurons that express Gαi-interacting protein (GINIP) promote tissue repair in a model of UV-induced skin damage by secreting the neuropeptide TAFA4, which regulates skin-resident macrophages to release IL-10 and limit fibrosis.
- Guillaume Hoeffel
- , Guilhaume Debroas
- & Sophie Ugolini
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Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Meningeal lymphatic drainage can affect the microglial inflammatory response and anti-amyloid-β immunotherapy in mouse models of Alzheimer’s disease.
- Sandro Da Mesquita
- , Zachary Papadopoulos
- & Jonathan Kipnis
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Restoring metabolism of myeloid cells reverses cognitive decline in ageing
In aged mice, inhibition of prostaglandin E2 (PGE2) signalling through its receptor EP2 improves cellular bioenergetics, reduces inflammatory responses and restores hippocampal plasticity to youthful levels, resulting in an improvement in spatial memory and cognition.
- Paras S. Minhas
- , Amira Latif-Hernandez
- & Katrin I. Andreasson
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Local immune response to food antigens drives meal-induced abdominal pain
In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.
- Javier Aguilera-Lizarraga
- , Morgane V. Florens
- & Guy E. Boeckxstaens
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STING controls nociception via type I interferon signalling in sensory neurons
Studies using mouse and non-human primate models identify the innate immune regulator STING—acting via type I interferons—as a key regulator of nociception, suggesting new targets for the treatment of chronic pain.
- Christopher R. Donnelly
- , Changyu Jiang
- & Ru-Rong Ji
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Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes
A subpopulation of astrocytes characterized by the expression of LAMP1 and TRAIL limits inflammation in the central nervous system through a mechanism involving the microbiota-modulated expression of IFNγ in meningeal natural killer cells.
- Liliana M. Sanmarco
- , Michael A. Wheeler
- & Francisco J. Quintana
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Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis
In adult mice, astrocytes carry out phagocytosis of excitatory hippocampal synapses through MEGF10 to maintain synaptic and circuit homeostasis.
- Joon-Hyuk Lee
- , Ji-young Kim
- & Won-Suk Chung
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Gut-educated IgA plasma cells defend the meningeal venous sinuses
IgA-secreting plasma cells that originate in the intestine are found in the meninges, where they protect the brain against pathogens.
- Zachary Fitzpatrick
- , Gordon Frazer
- & Menna R. Clatworthy
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Negative feedback control of neuronal activity by microglia
Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.
- Ana Badimon
- , Hayley J. Strasburger
- & Anne Schaefer
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C9orf72 in myeloid cells suppresses STING-induced inflammation
Studies of mice and humans suggest a role for loss of the C9orf72 protein in some neurodegenerative disorders: with reduced C9orf72 levels, there is more inflammation mediated by the STING protein in immune and brain cells.
- Madelyn E. McCauley
- , Jacqueline Gire O’Rourke
- & Robert H. Baloh
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Microbiota modulate sympathetic neurons via a gut–brain circuit
A combination of gnotobiotic mouse models, transcriptomics, circuit tracing and chemogenetic manipulations identifies neuronal circuits that integrate microbial signals in the gut with regulation of the sympathetic nervous system.
- Paul A. Muller
- , Marc Schneeberger
- & Daniel Mucida
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The liver–brain–gut neural arc maintains the Treg cell niche in the gut
A liver–brain–gut neural circuit responds to the gut microenvironment and regulates the activity of peripheral regulatory T cells in the colon by controlling intestinal antigen-presenting cells in a muscarinic signalling-dependent manner.
- Toshiaki Teratani
- , Yohei Mikami
- & Takanori Kanai