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https://www.readbyqxmd.com/read/27608759/lymphatics-in-neurological-disorders-a-neuro-lympho-vascular-component-of-multiple-sclerosis-and-alzheimer-s-disease
#1
REVIEW
Antoine Louveau, Sandro Da Mesquita, Jonathan Kipnis
Lymphatic vasculature drains interstitial fluids, which contain the tissue's waste products, and ensures immune surveillance of the tissues, allowing immune cell recirculation. Until recently, the CNS was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy...
September 7, 2016: Neuron
https://www.readbyqxmd.com/read/27540163/multifaceted-interactions-between-adaptive-immunity-and-the-central-nervous-system
#2
REVIEW
Jonathan Kipnis
Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence...
August 19, 2016: Science
https://www.readbyqxmd.com/read/27460561/how-do-meningeal-lymphatic-vessels-drain-the-cns
#3
REVIEW
Daniel Raper, Antoine Louveau, Jonathan Kipnis
The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood...
September 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27409813/unexpected-role-of-interferon-%C3%AE-in-regulating-neuronal-connectivity-and-social-behaviour
#4
Anthony J Filiano, Yang Xu, Nicholas J Tustison, Rachel L Marsh, Wendy Baker, Igor Smirnov, Christopher C Overall, Sachin P Gadani, Stephen D Turner, Zhiping Weng, Sayeda Najamussahar Peerzade, Hao Chen, Kevin S Lee, Michael M Scott, Mark P Beenhakker, Vladimir Litvak, Jonathan Kipnis
Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses...
July 21, 2016: Nature
https://www.readbyqxmd.com/read/27402496/central-nervous-system-immunological-ivory-tower-or-not
#5
Ioana A Marin, Jonathan Kipnis
The view of the nervous system being the victim of destructive inflammation during autoimmunity, degeneration, or injury has been rapidly changing. Recent studies are supporting the idea that the immune system provides support for the nervous system at various levels. Though cell patrolling through the nervous system parenchyma is limited compared with other tissues, immune cell presence within the central nervous system (CNS; microglia), as well as around it (in the meningeal spaces and choroid plexus) has been shown to be important for brain tissue maintenance and function...
January 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27096312/bugs-and-brain-how-infection-makes-you-feel-blue
#6
COMMENT
Jasmin Herz, Jonathan Kipnis
In this issue of Immunity, Prinz and colleagues (2016) describe an unexpected mechanism underlying the role of type I interferon in the initiation of cognitive impairment and sickness behavior during viral infection through induction of chemokine CXCL10 in central nervous system epithelial and endothelial cells.
April 19, 2016: Immunity
https://www.readbyqxmd.com/read/26909581/corrigendum-structural-and-functional-features-of-central-nervous-system-lymphatic-vessels
#7
Antoine Louveau, Igor Smirnov, Timothy J Keyes, Jacob D Eccles, Sherin J Rouhani, J David Peske, Noel C Derecki, David Castle, James W Mandell, Kevin S Lee, Tajie H Harris, Jonathan Kipnis
No abstract text is available yet for this article.
May 12, 2016: Nature
https://www.readbyqxmd.com/read/26858363/shedding-light-on-il-33-in-the-eye
#8
COMMENT
Sachin P Gadani, Jonathan Kipnis
No abstract text is available yet for this article.
February 8, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26814583/natural-killers-in-the-brain-s-nursery
#9
COMMENT
Sachin P Gadani, Jonathan Kipnis
No abstract text is available yet for this article.
February 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/26775912/understanding-the-role-of-t-cells-in-cns-homeostasis
#10
REVIEW
Erik Ellwardt, James T Walsh, Jonathan Kipnis, Frauke Zipp
T cells within the central nervous system (CNS) have been generally considered pathogenic, especially in the context of neuroinflammatory disease. However, recent findings have revealed varied functions for T cells in the healthy CNS, as well as more complex roles for these cells in infection and injury than previously appreciated. Here we review evidence indicating important roles for different T cell subsets in the maintenance of CNS homeostasis. We examine the contribution of T cells in limiting inflammation and damage upon CNS injury, infection, and in neurodegeneration, and discuss the current understanding of the cellular and molecular mechanisms involved...
February 2016: Trends in Immunology
https://www.readbyqxmd.com/read/26431936/revisiting-the-mechanisms-of-cns-immune-privilege
#11
REVIEW
Antoine Louveau, Tajie H Harris, Jonathan Kipnis
Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders...
October 2015: Trends in Immunology
https://www.readbyqxmd.com/read/26248266/breaking-bad-blood-%C3%AE-2-microglobulin-as-a-pro-aging-factor-in-blood
#12
COMMENT
Anthony J Filiano, Jonathan Kipnis
No abstract text is available yet for this article.
August 2015: Nature Medicine
https://www.readbyqxmd.com/read/26139369/dealing-with-danger-in-the-cns-the-response-of-the-immune-system-to-injury
#13
REVIEW
Sachin P Gadani, James T Walsh, John R Lukens, Jonathan Kipnis
Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival. Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS. The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS. In this review, we describe the temporal sequence of immunological events that follow CNS injury...
July 1, 2015: Neuron
https://www.readbyqxmd.com/read/26030524/structural-and-functional-features-of-central-nervous-system-lymphatic-vessels
#14
Antoine Louveau, Igor Smirnov, Timothy J Keyes, Jacob D Eccles, Sherin J Rouhani, J David Peske, Noel C Derecki, David Castle, James W Mandell, Kevin S Lee, Tajie H Harris, Jonathan Kipnis
One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses...
July 16, 2015: Nature
https://www.readbyqxmd.com/read/25982834/unexpected-cellular-players-in-rett-syndrome-pathology
#15
REVIEW
James C Cronk, Noel C Derecki, Vladimir Litvak, Jonathan Kipnis
Rett syndrome is a devastating neurodevelopmental disorder, primarily caused by mutations of methyl CpG-binding protein 2 (MeCP2). Although the genetic cause of disease was identified over a decade ago, a significant gap still remains in both our clinical and scientific understanding of its pathogenesis. Neurons are known to be primary players in pathology, with their dysfunction being the key in Rett syndrome. While studies in mice have demonstrated a clear causative - and potential therapeutic - role for neurons in Rett syndrome, recent work has suggested that other tissues also contribute significantly to progression of the disease...
August 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/25938785/mhcii-independent-cd4-t-cells-protect-injured-cns-neurons-via-il-4
#16
James T Walsh, Sven Hendrix, Francesco Boato, Igor Smirnov, Jingjing Zheng, John R Lukens, Sachin Gadani, Daniel Hechler, Greta Gölz, Karen Rosenberger, Thomas Kammertöns, Johannes Vogt, Christina Vogelaar, Volker Siffrin, Ali Radjavi, Anthony Fernandez-Castaneda, Alban Gaultier, Ralf Gold, Thirumala-Devi Kanneganti, Robert Nitsch, Frauke Zipp, Jonathan Kipnis
No abstract text is available yet for this article.
June 2015: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/25902482/methyl-cpg-binding-protein-2-regulates-microglia-and-macrophage-gene-expression-in-response-to-inflammatory-stimuli
#17
James C Cronk, Noël C Derecki, Emily Ji, Yang Xu, Aaron E Lampano, Igor Smirnov, Wendy Baker, Geoffrey T Norris, Ioana Marin, Nathan Coddington, Yochai Wolf, Stephen D Turner, Alan Aderem, Alexander L Klibanov, Tajie H Harris, Steffen Jung, Vladimir Litvak, Jonathan Kipnis
Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice...
April 21, 2015: Immunity
https://www.readbyqxmd.com/read/25898188/brainless-immunity-no-more
#18
COMMENT
Sachin P Gadani, Jonathan Kipnis
No abstract text is available yet for this article.
May 2015: Nature Immunology
https://www.readbyqxmd.com/read/25661185/the-glia-derived-alarmin-il-33-orchestrates-the-immune-response-and-promotes-recovery-following-cns-injury
#19
Sachin P Gadani, James T Walsh, Igor Smirnov, Jingjing Zheng, Jonathan Kipnis
Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment...
February 18, 2015: Neuron
https://www.readbyqxmd.com/read/25607842/mhcii-independent-cd4-t-cells-protect-injured-cns-neurons-via-il-4
#20
James T Walsh, Sven Hendrix, Francesco Boato, Igor Smirnov, Jingjing Zheng, John R Lukens, Sachin Gadani, Daniel Hechler, Greta Gölz, Karen Rosenberger, Thomas Kammertöns, Johannes Vogt, Christina Vogelaar, Volker Siffrin, Ali Radjavi, Anthony Fernandez-Castaneda, Alban Gaultier, Ralf Gold, Thirumala-Devi Kanneganti, Robert Nitsch, Frauke Zipp, Jonathan Kipnis
A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion...
February 2015: Journal of Clinical Investigation
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