The immunomodulatory oligodendrocyte

Zeis, Thomas; Enz, Lukas; Schaeren-Wiemers, Nicole

doi:10.1016/j.brainres.2015.09.021

Cited by 86 publications

(67 citation statements)

References 97 publications

(103 reference statements)

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“…Homeostatic glial activation can beneficial in dealing with minor tissue dysfunction, but it can also become pathogenic if the activation is persistent 20 . Though oligodendrocytes have recently been suggested to participate in immune responses 21 , imaging methods are currently only available for microglia and astrocyte imaging in humans, and thus we will focus on techniques targeting these cells. Future efforts will hopefully lead to cell-specific imaging strategies for all CNS immunocompetent cells.…”

Section: Imaging Resident Immunocompetent Cellsmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

175

146

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Neuroinflammation is implicated in the pathophysiology of a growing number of human disorders, including multiple sclerosis, chronic pain, traumatic brain injury, and amyotrophic lateral sclerosis. As a result, interest in the development of novel methods to investigate neuroinflammatory processes, for the purpose of diagnosis, development of new therapies, and treatment monitoring, has surged over the past 15 years. Neuroimaging offers a wide array of non- or minimally invasive techniques to characterize neuroinflammatory processes. The intent of this Review is to provide brief descriptions of currently available neuroimaging methods to image neuroinflammation in the human central nervous system (CNS) in vivo. Specifically, because of the relatively widespread accessibility of equipment for nuclear imaging (positron emission tomography [PET]; single photon emission computed tomography [SPECT]) and magnetic resonance imaging (MRI), we will focus on strategies utilizing these technologies. We first provide a working definition of “neuroinflammation” and then discuss available neuroimaging methods to study human neuroinflammatory processes. Specifically, we will focus on neuroimaging methods that target (1) the activation of CNS immunocompetent cells (e.g. imaging of glial activation with TSPO tracer [11C]PBR28), (2) compromised BBB (e.g. identification of MS lesions with gadolinium-enhanced MRI), (3) CNS-infiltration of circulating immune cells (e.g. tracking monocyte infiltration into brain parenchyma with iron oxide nanoparticles and MRI), and (4) pathological consequences of neuroinflammation (e.g. imaging apoptosis with [99mTc]Annexin V or iron accumulation with T2* relaxometry). This Review provides an overview of state-of-the-art techniques for imaging human neuroinflammation which have potential to impact patient care in the foreseeable future.

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Section: Imaging Resident Immunocompetent Cellsmentioning

confidence: 99%

In Vivo Imaging of Human Neuroinflammation

Albrecht¹,

Granziera

Hooker³

et al. 2016

ACS Chem. Neurosci.

175

146

View full text Add to dashboard Cite

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“…To better define the role of glial cells in ECM development, we further investigated oligodendrocytes, recently recognized as CNS immunomodulatory cells, rather than “defenseless victims” of brain inflammation caused by microglia activation [41], since oligodendrocytes express a wide range of immunomodulatory molecules (reviewed in [42]). Immunofluorescence staining was performed on brain of WT and ST2 -/- infected mice, and compared to naïve mice, to evaluate IL-33 production by oligodendrocyte after Pb A-infection (Fig 6A and 6B).…”

Section: Resultsmentioning

confidence: 99%

“…Microglia, considered as the classical innate immune cells of the CNS, may impact oligodendrocyte function (reviewed in [42]). Indeed, a recent study reported oligodendrocyte damage after IL-1β stimulation in vitro [43].…”

Section: Resultsmentioning

confidence: 99%

IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria

et al. 2017

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Cerebral malaria (CM) is associated with a high mortality rate and long-term neurocognitive impairment in survivors. The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA)-infection reproduces several of these features. We reported recently increased levels of IL-33 protein in brain undergoing ECM and the involvement of IL-33/ST2 pathway in ECM development. Here we show that PbA-infection induced early short term and spatial memory defects, prior to blood brain barrier (BBB) disruption, in wild-type mice, while ST2-deficient mice did not develop cognitive defects. PbA-induced neuroinflammation was reduced in ST2-deficient mice with low Ifng, Tnfa, Il1b, Il6, CXCL9, CXCL10 and Cd8a expression, associated with an absence of neurogenesis defects in hippocampus. PbA-infection triggered a dramatic increase of IL-33 expression by oligodendrocytes, through ST2 pathway. In vitro, IL-33/ST2 pathway induced microglia expression of IL-1β which in turn stimulated IL-33 expression by oligodendrocytes. These results highlight the IL-33/ST2 pathway ability to orchestrate microglia and oligodendrocytes responses at an early stage of PbA-infection, with an amplification loop between IL-1β and IL-33, responsible for an exacerbated neuroinflammation context and associated neurological and cognitive defects.

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“…For example, gliosis may occur independent of evident axonal pathology and vice versa low-grade gliosis is not necessarily detrimental to axons or myelin, as seen in mice lacking the myelin protein tetraspanin-2 (de Monasterio-Schrader et al, 2013). Indeed, immune cells may be modulated by axonal pathology as well as by oligodendroglial molecules (Zeis, Enz, & Schaeren-Wiemers, 2016). On the other hand, we are not aware of in vivo evidence indicating a direct role for activated microglia or astrocytes in enhancing axonal pathology in SPG2/PMD spectrum disorders.…”

Section: Discussionmentioning

confidence: 99%

Genetic dissection of oligodendroglial and neuronalPlp1function in a novel mouse model of spastic paraplegia type 2

Lüders

Patzig

Simons

et al. 2017

Glia

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Proteolipid protein (PLP) is the most abundant integral membrane protein in compact central nervous system myelin, and null mutations of the PLP1 gene cause spastic paraplegia type 2 (SPG2). SPG2 patients and PLP-deficient mice exhibit only moderate abnormalities of myelin but progressive degeneration of long axons. Since Plp1 gene products are detected in a subset of neurons it has been suggested that the loss of neuronal Plp1 expression could be the cause of the axonal pathology. To test this hypothesis, we created mice with a floxed Plp1 allele for selective Cre-mediated recombination in neurons. We find that recombination of Plp1 in excitatory projection neurons does not cause neuropathology, whereas oligodendroglial targeting of Plp1 is sufficient to cause the entire neurodegenerative spectrum of SPG2 including axonopathy and secondary neuroinflammation. We conclude that PLP-dependent loss of oligodendroglial support is the primary cause of axonal degeneration in SPG2.

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The immunomodulatory oligodendrocyte

Cited by 86 publications

References 97 publications

In Vivo Imaging of Human Neuroinflammation

In Vivo Imaging of Human Neuroinflammation

IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria

Genetic dissection of oligodendroglial and neuronalPlp1function in a novel mouse model of spastic paraplegia type 2

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