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Special Issue "Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 6843

Special Issue Editors

Dr. Maria Liguori
E-Mail Website
Guest Editor
Consiglio Nazionale delle Ricerche, Institute of Biomedical Technologies, Bari Unit, Bari, Italy
Interests: neurosciences; multiple sclerosis; neurodegenerative diseases; genomics, transcriptomics; neuroimaging; genotype-phenotype correlations; pharmacogenomics
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Rosaria Coscia
E-Mail Website1 Website2 Website3
Co-Guest Editor
National Research Council of Italy, Institute of Biochemistry and Cell Biology, Via P. Castellino 111, 80131 Naples, Italy
Interests: comparative immunology; immunoglobulin genes; adaptive immunity; molecular biology; biochemistry; genome evolution; engineered monoclonal antibodies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

The term “Autoimmunity” describes the loss of immunological tolerance (central o peripheral) that allows to recognize its own cells and tissues as “self”; in humans, this leads to aberrant immune responses directed against healthy tissues and/or cells or cell components, resulting in diseases that may involve local (organ-specific, e.g. the central and/or peripheral nervous system) or systemic reactions.

At present, it is well known that there are several cellular and molecular mechanisms underlying autoimmunity (e.g. molecular mimicry, cytokine dysregulation, dendritic cell apoptosis and defective autophagy), in which different factors such as sex, genes and the environment can play different roles. In particular, since females have been reported to be more often affected by autoimmune diseases, the interest has been addressed towards the biological analysis of the observed sex-bias and its impact on immune-mediated diseases.

One of the most recognizable and studied autoimmune disease of the Central Nervous System is Multiple Sclerosis (MS), however several other syndromes have been rapidly recognized, depending on the target of the immunological reaction. Interestingly, sometimes the molecular mechanisms underlying these disorders are overlapping due to common pathogenic pathways. As examples, conditional deletions of autophagy-related proteins seem to protect from experimental autoimmune encephalomyelitis (the animal model of MS) and experimental arthritis. Furthermore, single nucleotide polymorphisms (SNPs) of autophagy-related genes were reported associated with the susceptibility to both systemic lupus erythematosus and Crohn's disease. In our view, also looking into these types of interactions will help to disentangle the complex regulation of autoimmuniy, and it will also provide a valuable support for addressing possible novel targeted therapeutic efforts.

In this Special Issue we aim to provide the whole picture of autoimmunity from a broad perspective, starting from the general molecular mechanisms and the novel hypotheses on its multifactorial background, to other more practical perspectives, such as the identification of potential biomarkers of the immune status associated with a given disease. Particular interest will be addressed to novel and original data reporting significant sex differences in the autoimmune pathogenic mechanisms of the most known neurological diseases.

Dr. Maria Liguori
Guest Editor
Dr. Maria Rosaria Coscia
Co-Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Molecular basis of immune mechanisms
  • Genetics and epigenetics of autoimmune diseases
  • Immune dysregulation
  • Sex differences of self-tolerance and other pathogenic mechanisms
  • Autoimmunity and neurodegeneration
  • Environmental modulation of immune response
  • Microbiome and Nervous Systems
  • Multiple Sclerosis and other autoimmune diseases
  • Immunotherapy
  • Biomarkers
  • Computational biology

Related Special Issue

Published Papers (6 papers)

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Research

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Article
PI3-Kinase p110α Deficiency Modulates T Cell Homeostasis and Function and Attenuates Experimental Allergic Encephalitis in Mature Mice
Int. J. Mol. Sci. 2021, 22(16), 8698; https://doi.org/10.3390/ijms22168698 - 13 Aug 2021
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Abstract
Class I phosphoinositide 3-kinases (PI3K) are involved in the development of normal and autoimmune responses, including Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for human multiple sclerosis (MS). Here, the role of the ubiquitously expressed class IA PI3K p110α catalytic subunits in EAE [...] Read more.
Class I phosphoinositide 3-kinases (PI3K) are involved in the development of normal and autoimmune responses, including Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for human multiple sclerosis (MS). Here, the role of the ubiquitously expressed class IA PI3K p110α catalytic subunits in EAE has been analyzed using a model of Cre/flox mediated T cell specific deletion of p110α catalytic chain (p110αΔT). Comparison of two month-old (young) and six month-old (mature) p110αΔT mice and their wild type (WT) counterparts indicated loss of spleen CD4+ T cells that increased with age, indicating a role of p110α in their homeostasis. In contrast, CD4+ T regulatory (Treg) cells were enhanced in mature p110αΔT mice when compared to WT mice. Since Myelin Oligodendrocyte Glycoprotein (MOG) peptide-induced EAE is dependent on, or mediated by CD4+ T cells and CD4+ T cell-derived cytokines and controlled by Treg cells, development of EAE in young and mature WT or p110αΔT mice was analyzed. EAE clinical symptoms and disease scores in six month p110αΔT mice were significantly lower than those of mature WT, or young WT and p110αΔT mice. Furthermore, ex vivo antigen activation of lymph node cells from MOG immunized mature p110αΔT mice induced significantly lower levels of IFN-γ and IL-17A than young p110αΔT or young and mature WT mice. Other cytokines including IL-2, IL-10 or TNF-α showed no significant differences between p110αΔT and WT mature mice. Our data show a lower incidence of MOG-induced EAE in mature p110αΔT mice linked to altered T cell homeostasis and lower secretion of inflammatory cytokines. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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Article
Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE
Int. J. Mol. Sci. 2021, 22(6), 2924; https://doi.org/10.3390/ijms22062924 - 13 Mar 2021
Cited by 1 | Viewed by 1247
Abstract
Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX’s effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 [...] Read more.
Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX’s effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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Article
Rapid Expansion of Virus-Specific CD4+ T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus
Int. J. Mol. Sci. 2020, 21(20), 7719; https://doi.org/10.3390/ijms21207719 - 19 Oct 2020
Cited by 1 | Viewed by 895
Abstract
The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is [...] Read more.
The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4+ T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4+ T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4+ T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4+ T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3+CD4+ T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3+CD4+ T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4+ T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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Review

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Review
NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases—Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome
Int. J. Mol. Sci. 2021, 22(17), 9520; https://doi.org/10.3390/ijms22179520 - 01 Sep 2021
Cited by 2 | Viewed by 1119
Abstract
NKT cells comprise three subsets—type I (invariant, iNKT), type II, and NKT-like cells, of which iNKT cells are the most studied subset. They are capable of rapid cytokine production after the initial stimulus, thus they may be important for polarisation of Th cells. [...] Read more.
NKT cells comprise three subsets—type I (invariant, iNKT), type II, and NKT-like cells, of which iNKT cells are the most studied subset. They are capable of rapid cytokine production after the initial stimulus, thus they may be important for polarisation of Th cells. Due to this, they may be an important cell subset in autoimmune diseases. In the current review, we are summarising results of NKT-oriented studies in major neurological autoimmune diseases—multiple sclerosis, myasthenia gravis, and Guillain-Barre syndrome and their corresponding animal models. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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Review
Neurological Immunotoxicity from Cancer Treatment
Int. J. Mol. Sci. 2021, 22(13), 6716; https://doi.org/10.3390/ijms22136716 - 23 Jun 2021
Cited by 6 | Viewed by 1150
Abstract
The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, [...] Read more.
The emergence of immune-based treatments for cancer has led to a growing field dedicated to understanding and managing iatrogenic immunotoxicities that arise from these agents. Immune-related adverse events (irAEs) can develop as isolated events or as toxicities affecting multiple body systems. In particular, this review details the neurological irAEs from immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell immunotherapies. The recognition and treatment of neurological irAEs has variable success, depending on the severity and nature of the neurological involvement. Understanding the involved mechanisms, predicting those at higher risk for irAEs, and establishing safety parameters for resuming cancer immunotherapies after irAEs are all important fields of ongoing research. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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Review
A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors
Int. J. Mol. Sci. 2021, 22(7), 3696; https://doi.org/10.3390/ijms22073696 - 02 Apr 2021
Cited by 2 | Viewed by 1009
Abstract
Multiple sclerosis is a complex, multifactorial, dysimmune disease prevalent in women. Its etiopathogenesis is extremely intricate, since each risk factor behaves as a variable that is interconnected with others. In order to understand these interactions, sex must be considered as a determining element, [...] Read more.
Multiple sclerosis is a complex, multifactorial, dysimmune disease prevalent in women. Its etiopathogenesis is extremely intricate, since each risk factor behaves as a variable that is interconnected with others. In order to understand these interactions, sex must be considered as a determining element, either in a protective or pathological sense, and not as one of many variables. In particular, sex seems to highly influence immune response at chromosomal, epigenetic, and hormonal levels. Environmental and genetic risk factors cannot be considered without sex, since sex-based immunological differences deeply affect disease onset, course, and prognosis. Understanding the mechanisms underlying sex-based differences is necessary in order to develop a more effective and personalized therapeutic approach. Full article
(This article belongs to the Special Issue Autoimmunity in the Nervous Systems: Multiple Sclerosis and Beyond)
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