0000000000141170
AUTHOR
Eva Reuter
Role of Sortilin in Models of Autoimmune Neuroinflammation
Abstract The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in…
A novel automated segmentation method for retinal layers in OCT images proves retinal degeneration after optic neuritis.
Aim The evaluation of inner retinal layer thickness can serve as a direct biomarker for monitoring the course of inflammatory diseases of the central nervous system such as multiple sclerosis (MS). Using optical coherence tomography (OCT), thinning of the retinal nerve fibre layer and changes in deeper retinal layers have been observed in patients with MS. Here, we first compare a novel method for automated segmentation of OCT images with manual segmentation using two cohorts of patients with MS. Using this method, we also aimed to reproduce previous findings showing retinal degeneration following optic neuritis (ON) in MS. Methods Based on a 5×5 expansion of the Prewitt operator to efficie…
Increased structural white and grey matter network connectivity compensates for functional decline in early multiple sclerosis
Background: The pathology of multiple sclerosis (MS) consists of demyelination and neuronal injury, which occur early in the disease; yet, remission phases indicate repair. Whether and how the central nervous system (CNS) maintains homeostasis to counteract clinical impairment is not known. Objective: We analyse the structural connectivity of white matter (WM) and grey matter (GM) networks to understand the absence of clinical decline as the disease progresses. Methods: A total of 138 relapsing–remitting MS patients (classified into six groups by disease duration) and 32 healthy controls were investigated using 3-Tesla magnetic resonance imaging (MRI). Networks were analysed using graph the…
Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.
Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8+T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmedin vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8+T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40–54 (MOG40–54) bothin vitroandin vivo. The aim of this study was to investigate whether such cross-recognizing CD8+T cells are capable of inducing CNS damagein vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, …
The role of CD8+ T cells and their local interaction with CD4+ T cells in myelin oligodendrocyte glycoprotein35-55-induced experimental autoimmune encephalomyelitis.
Abstract T cells have an essential role in the induction of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Although for CD4+ T cells it is well established that they contribute to the disease, less is known about the role of CD8+ T cells. Our aim was to determine the individual contribution of CD4+ and CD8+ T cells in myelin oligodendrocyte glycoprotein (MOG)35–55–induced EAE. We investigated MOG35–55–activated CD8+ T cells to clarify their potential to induce or attenuate EAE. We monitored the behavior of CD8+ T cells and their interaction with CD4+ T cells directly at the site of inflammation in the CNS using intravital imaging of the brainstem of…
The role of NFATc2 in chronic autoimmune neuroinflammation
Dimethyl fumarate (DMF), a fumaric acid ester with potential immunomodulatory and neuroprotective effect, was recently approved as treatment for relapsing–remitting multiple sclerosis (MS). DMF ameliorates the clinical course of experimental autoimmune encephalomyelitis (EAE), the murine model of MS, where it exerts a neuroprotective action, reducing demyelination and axonal loss. We hypothesized that these effects are mediated, at least in part, through its action on microglia. We used a microglial cell line (N9) activated with lipopolysaccharide (LPS) to analyze the effect of monomethyl fumarate (MMF), a bioactive metabolite of DMF, in vitro. We show that MMF reverts the molecular phenoty…
Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis
Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered. DCs facilitate iTreg induction by creating a milieu with high levels of interleukin (IL)-2 due to a st…