Neuroinflammation in Autoimmune Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 June 2023) | Viewed by 4888

Special Issue Editor


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Guest Editor
Centre for Genomics and Oncological Research (GENYO), Pfizer-University of Granada-Andalusian Regional Government, 18016 Granada, Spain
Interests: animal models; autoimmune diseases; animal behaviors; microglia; neuroinflammation; central nervous system

Special Issue Information

Dear Colleagues,

The Central Nervous System (CNS) has been considered for many years an immune-privileged organ. Currently, we know that there is a tight immune regulation to maintain CNS homeostasis and avoid cell damage and loss of function. Leukocytes,  B and T cells,  can enter in the CNS by extravasation from the cerebrospinal fluid (CSF). The activation of neuroinflammatory processes by different triggers include the secretion of cytokines and chemokines by the immune mediators of CNS mainly microglia and astrocytes, but also neurons. These events can have consequences affecting neural behavior but the mechanisms involved are far to be known.

In the last few decades, interest for the interaction between peripheral immune response and CNS has been growing. In systemic autoimmune diseases (SADs), the immune deregulation can affect the central and peripheral nervous systems. CNS alterations are relatively common in these patients and, as a result, they present highly diverse neurological manifestations such as psychosis, cognitive dysfunction, headaches, depression, vasculitis, etc., but it is difficult to determine if the neurological manifestations are a primary event or secondary due to systemic autoimmunity.

Animal models are highly valuable tools to study  autoimmune and neuroinflammatory diseases and how they affect the animal behavior. They allow us to follow disease development at immunological and neurological levels, and to combine cell, molecular and histological studies with behavior analysis. Preclinical models also allow us to test new treatments or evaluate how actual treatments affect neural behavior. The elucidation of the mechanisms, molecular pathways and cell types involved in the neurioinflammatory processes will allow us to improve actual treatments and life quality of those patients affected by autoimmune diseases that course with neurological complications.

This Special Issue is focused on the study of neuroinflammatory processes that have a place in autoimmune diseases, including  the activation of the immune response locally in CNS, interaction between the peripheral immune system and the CNS and the evaluation of the consequences that these processes have in the behaviors. It is crucial to understand cross-talk between the CNS and the immune system  and  to elucidate mechanisms involved in neurodegenerative events to develop new therapeutic strategies or improve the existing treatments of autoimmune diseases with neurological components.

Dr. María Morell Hita
Guest Editor

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Keywords

  • autoantibodies
  • cytokines
  • microglia
  • astrocytes
  • neuron
  • toll-like receptors
  • type I interferon
  • immune infiltrates
  • behavior
  • animal models

Published Papers (2 papers)

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14 pages, 1865 KiB  
Article
Primary Cortical Cell Tri-Culture-Based Screening of Neuroinflammatory Response in Toll-like Receptor Activation
by Noah Goshi, Hyehyun Kim and Erkin Seker
Biomedicines 2022, 10(9), 2122; https://doi.org/10.3390/biomedicines10092122 - 29 Aug 2022
Cited by 3 | Viewed by 2174
Abstract
The activation of toll-like receptors (TLRs) in the central nervous system (CNS) can lead to neuroinflammation and contribute to many neurological disorders, including autoimmune diseases. Cell culture models are powerful tools for studying specific molecular and cellular mechanisms that contribute to these disease [...] Read more.
The activation of toll-like receptors (TLRs) in the central nervous system (CNS) can lead to neuroinflammation and contribute to many neurological disorders, including autoimmune diseases. Cell culture models are powerful tools for studying specific molecular and cellular mechanisms that contribute to these disease states and identifying potential therapeutics. However, most cell culture models have limitations in capturing biologically relevant phenomena, due in part to the non-inclusion of necessary cell types. Neurons, astrocytes, and microglia (critical cell types that play a role in neuroinflammation) all express at least a subset of TLRs. However, the response of each of these cell types to various TLR activation, along with their relative contribution to neuroinflammatory processes, is far from clear. In this study, we demonstrate the screening capabilities of a primary cortical cell tri-culture of neuron, astrocyte, and microglia from neonatal rats. Specifically, we compare the neuroinflammatory response of tri-cultures to that of primary neuron-astrocyte co-cultures to a suite of known TLR agonists. We demonstrate that microglia are required for observation of neurotoxic neuroinflammatory responses, such as increased cell death and apoptosis, in response to TLR2, 3, 4, and 7/8 activation. Additionally, we show that following TLR3 agonist treatment, microglia and astrocytes play opposing roles in the neuroinflammatory response, and that the observed response is dictated by the degree of TLR3 activation. Overall, we demonstrate that microglia play a significant role in the neuroinflammatory response to TLR activation in vitro and, hence, the tri-culture has the potential to serve as a screening platform that better replicates the in vivo responses. Full article
(This article belongs to the Special Issue Neuroinflammation in Autoimmune Diseases)
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13 pages, 1841 KiB  
Systematic Review
Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis
by Moritz Förster, Christopher Nelke, Saskia Räuber, Hans Lassmann, Tobias Ruck, Maria Pia Sormani, Alessio Signori, Hans-Peter Hartung, Patrick Küry, Sven G. Meuth and David Kremer
Biomedicines 2021, 9(12), 1899; https://doi.org/10.3390/biomedicines9121899 - 14 Dec 2021
Cited by 3 | Viewed by 2235
Abstract
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal [...] Read more.
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis. Full article
(This article belongs to the Special Issue Neuroinflammation in Autoimmune Diseases)
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