Role of immune gene variants in multiple sclerosis susceptibility and severity: Genetic burden consequences on immune cell functionality

2014 ◽  
Vol 275 (1-2) ◽  
pp. 50
Author(s):  
Mohamed El Behi ◽  
Vincent Damotte ◽  
Lena Guillot-nöel ◽  
Violetta Zujovic ◽  
Isabelle Rebeix ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Immune Gene ◽  
Gene Variants ◽  
Multiple Sclerosis Susceptibility ◽  
Genetic Burden ◽  
Cell Functionality

scholarly journals Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

2021 ◽  
Vol 22 (17) ◽  
pp. 9460
Author(s):  
Helmut Segner ◽  
Christyn Bailey ◽  
Carolina Tafalla ◽  
Jun Bo
Keyword(s):  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Disease Susceptibility ◽  
Immune Cell ◽  
Physiological Role ◽  
Immune Gene ◽  
Immune Systems ◽  
Aryl Hydrocarbon ◽  
The Impact

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

scholarly journals Acetate correlates with disability and immune response in multiple sclerosis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10220 ◽  
Author(s):  
Silvia Pérez-Pérez ◽  
María Inmaculada Domínguez-Mozo ◽  
Aitana Alonso-Gómez ◽  
Silvia Medina ◽  
Noelia Villarrubia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Short Chain Fatty Acids ◽  
Liquid Chromatography Mass Spectrometry ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Disability Status

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e–4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e–4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r =  − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

The interleukin-1 gene family in multiple sclerosis susceptibility and disease course

2003 ◽  
Vol 9 (6) ◽  
pp. 535-539 ◽  
Author(s):  
Tineke Hooper-van Veen ◽  
Hans M Schrijver ◽  
Antoon Zwiers ◽  
J Bart A Crusius ◽  
Dirk L Knol ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gene Polymorphisms ◽  
Interleukin 1 ◽  
Progression Rate ◽  
Disease Course ◽  
Resonance Imaging ◽  
Multiple Sclerosis Susceptibility ◽  
Specific Allele ◽  
Magnetic Resonance Imaging Mri

Multiple sclerosis (MS) is a chronic disease of presumed autoimmune origin with a considerable polygenic influence. We have previously observed that a specific allele combination in genes of the interleukin-1 (IL-1) family influenced the progression rate in MS. We have considerably expanded our patient population (492 MS patients and 228 controls). In the present study, we investigated the role of the IL- 1A - 889, IL-1B - 511, IL-1B+3953 and IL-1RN VNTR gene polymorphisms in MS. In addition, we performed preliminary analyses on longitudinal magnetic resonance imaging (MRI) data. We found no associations between the polymorphisms and susceptibility to MS or clinical features. In addition, we observed no significant effect of the polymorphisms on brain or lesion volumes, Based on our data and those from the literature, one can conclude that there is currently no evidence to support a role for the IL-1 genes in MS.

scholarly journals Impact of Exercise on Immunometabolism in Multiple Sclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Benefits ◽  
Demyelinating Lesions ◽  
Inflammatory State ◽  
Autoimmune Condition ◽  
The Central Nervous System ◽  
Axonal Degradation

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.

The role of MEFV gene mutations in Multiple Sclerosis susceptibility

2010 ◽  
Vol 298 (1-2) ◽  
pp. 163
Author(s):  
Hamid Zahednasab ◽  
Mohammad Saadatnia ◽  
M. Reza Jabalameli ◽  
Seyed Amir Bahreini
Keyword(s):  
Multiple Sclerosis ◽  
Mefv Gene ◽  
Gene Mutations ◽  
Multiple Sclerosis Susceptibility

Deep characterization of paired chromatin and transcriptomes in four immune cell types from multiple sclerosis patients

Epigenomics ◽  
2021 ◽  
Author(s):  
Sunjay Jude Fernandes ◽  
Matilda Ericsson ◽  
Mohsen Khademi ◽  
Maja Jagodic ◽  
Tomas Olsson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Primary Role ◽  
Nucleotide Polymorphisms ◽  
Multiple Sclerosis Patients ◽  
Accessible Chromatin

Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-seq profiles from sorted blood immune CD4+ and CD8+ T cells, CD14+ monocytes and CD19+ B cells from healthy controls (HCs) and MS patients. Results: We identified differentially accessible regions between MS and HCs, primarily in CD4+ and CD19+. CD4+ regions were enriched for MS-associated single nucleotide polymorphisms and differentially methylated loci. In the vicinity of differentially accessible regions of CD4+ cells, 42 differentially expressed genes were identified. The top two dysregulated genes identified in this multilayer analysis were CCDC114 and SERTAD1. Conclusion: These findings provide new insight into the primary role of CD4+ and CD19+ cells in MS.

Lack of evidence for a role of the myelin basic protein gene in multiple sclerosis susceptibility in Sardinian patients

2002 ◽  
Vol 249 (11) ◽  
pp. 1552-1555 ◽  
Author(s):  
Eleonora Cocco ◽  
Cristina Mancosu ◽  
Elisabetta Fadda ◽  
Maria Rita Murru ◽  
Gianna Costa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Protein Gene ◽  
Multiple Sclerosis Susceptibility ◽  
Myelin Basic Protein Gene

scholarly journals Extra-hematopoietic immunomodulatory role of the SCID-susceptibility gene DOCK-2 identified by stepwise maturation of human iPSCs into clonogenic mesodermal stromal progenitors

2020 ◽  
Author(s):  
Cornelia Scharler ◽  
Rodolphe Poupardin ◽  
Patricia Peking ◽  
Martin Wolf ◽  
Gabriele Brachtl ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Immune Cell ◽  
Severe Combined Immunodeficiency ◽  
Susceptibility Gene ◽  
Stromal Fibroblast ◽  
Immune Gene ◽  
Hematopoietic Stem ◽  
Human Ipscs ◽  
Immunomodulatory Capacity

ABSTRACTStromal cells contribute to organ integrity as fibroblasts and to vascular stability as pericytes, in addition to their enigmatic niche function in many tissues. Their inherent immunomodulatory capacity attracted particular attention, initiating numerous clinical trials, particularly testing trophic regeneration and immunomodulation. Key stromal immune functions are still enigmatic.Here we show that dedicator of cytokinesis (DOCK-2) previously described for causing immune cell dysfunction plays a role in extra-hematopoietic immunity by regulating stromal/fibroblast immunomodulatory function. We used three independent strategies including iPSC-derived mesodermal stromal cell (MSC) lineage maturation, severe combined immunodeficiency (SCID) patient-derived cells and CRISPR/Cas9 knockout to support our findings.Human induced pluripotent stem cells (iPSCs) were generated from healthy bone marrow and umbilical cord blood-derived fibroblasts by Sendai virus-mediated transient expression of Yamanaka factors. After mesoderm induction, stromal differentiation was induced by platelet-derived growth factors under animal serum-free conditions. Under feeder-free defined conditions, iPSCs differentiated into expandable and cryo-preservable CD73+/CD105+/Tra-1-81− early iPS-MSCs lacking immunosuppressive potential. Successive maturation was required for reaching the canonical MSC phenotype and immunomodulatory competence over time, while maintaining clonogenicity, comparable to parental MSCs. Sequential RNAseq revealed acquisition of a spectrum of immune-related genes significantly expressed in mature iPS-MSCs and resembling parental MSC’s immune gene expression. The DOCK-2 gene attracted our attention because mutations can cause SCID. Interestingly, SCID patient-derived fibroblast lines harboring bi-allelic DOCK-2 mutations showed significantly reduced immunomodulatory capacity compared to non-mutated control fibroblasts. CRISPR/Cas9-mediated DOCK-2 knockout in healthy iPSCs resulted in iPS-MSCs that also displayed reduced immunomodulatory capacity, thus confirming a role of DOCK-2 in stromal immune function. At a mechanistic level, DOCK-2 deficiency resulted in disturbed subcellular localization of CDC42.This provides first evidence for an extra-hematopoietic immunomodulatory role of DOCK-2 in stromal cells, previously considered restricted to hampering immune cell migration/function resulting in SCID. We may speculate that some of the signs and symptoms of persisting immune disease after successful hematopoietic stem cell transplantation in SCID patients could at least in part be due to mutations, like DOCK-2−/−, permissive outside the hematopoietic immune system, as evidenced also by the increased virus infection susceptibility of DOCK-2 deficient fibroblasts.

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