Current knowledge on multiple sclerosis pathophysiology, disability progression assessment and treatment options, and the role of autologous hematopoietic stem cell transplantation

Gakis, Georgios; Angelopoulos, Ioannis; Panagoulias, Ioannis; Mouzaki, Athanasia

doi:10.1016/j.autrev.2023.103480

Cited by 3 publications

(3 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 Notably, RNAs from these DNA viruses (e.g., Epstein-Barr virus (EBV)) also produce RNAs with 5′-pppA termini, which could be highly immunogenic. 51 In addition, autoimmune diseases linked to EBV include systemic lupus erythematosus, 52 multiple sclerosis, 53 or rheumatoid arthritis. 54 It is suggested that EBV may contribute to the onset or exacerbation of autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

RNA 5ʹ terminal nucleotide determines the strength of the RIG-I/IFN signaling pathway

Wolczyk,

Szymanski,

Trus

et al. 2023

Preprint

View full text Add to dashboard Cite

The interferon (IFN) response is crucial for antiviral activity, but its overstimulation can lead to a wide range of autoimmune disorders. The cytoplasmic pattern recognition receptor RIG-I detects viral RNAs and endogenous polymerase III transcripts carrying a 5′-triphosphate (5′- ppp) or 5′-diphosphate (5′-pp) moiety, triggering an IFN immune response. While many viral RNAs initiate with 5′-ppp-adenosine (5′-pppA) and most endogenous Pol III transcripts in higher eukaryotes start with 5′-ppp-guanosine (5′-pppG), no apparent reason for this bias has been identified so far. Here we demonstrate that RNAs initiating with 5′-pppA trigger a much stronger RIG-I/IFN response than those starting with 5′-pppG. The structures of the matching RNA pairs have been confirmed to be similar, suggesting that functional differences in RIG-I/IFN pathway stimulation cannot be primarily explained by an altered conformation. We show that several GTP-binding proteins interact with 5′-pppG RNAs creating a steric hindrance and protecting these RNAs from activating RIG-I. Our findings suggest that 5′-pppG RNAs may allow some RNA viruses and Pol III transcripts to evade detection by cellular immune sensors. These results provide a new insight into the mechanism of sequence-dependent RIG-I/IFN pathway activation and have significant implications for understanding the antiviral response to RNA viruses and the contribution of Pol III-derived RNAs to autoimmune disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

RNA 5ʹ terminal nucleotide determines the strength of the RIG-I/IFN signaling pathway

Wolczyk,

Szymanski,

Trus

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Ten patients diagnosed with RRMS [ 1 ] and 10 healthy control subjects participated in the study ( Table 1 ). All study participants donated peripheral blood, which was used for preliminary experiments to establish the experimental protocols described in this study.…”

Section: Methodsmentioning

confidence: 99%

“…A reduced number or dysfunctional regulatory cells, especially CD4+CD25+Foxp3+ T regulatory cells (Tregs), overactive effector CD4+ helper T (Th) cells, especially Th1 and Th17, CD8+ cytotoxic T cells, autoantibody production and activated antigen-presenting cells (APCs), including dendritic cells (DCs), play a critical role in mediating an inflammatory milieu that leads to an autoimmune attack on intrinsic protein components within the myelin sheath. This leads to axonal damage and neurodegeneration [ 1 ]. The best-characterized autoantigens in MS are myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein (MOG)35–55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis

Rodi,

de Lastic,

Panagoulias

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35–55 (OM-MOG35–55) in vivo (EAE mouse model) and in vitro (human peripheral blood) and demonstrated that OM-MOG35–55 suppresses antigen-specific T cell responses associated with autoimmune demyelination. Based on these results, we developed different types of dendritic cells (DCs) from the peripheral blood monocytes of patients with multiple sclerosis (MS) or healthy controls presenting OM-MOG35–55 or MOG-35–55 to autologous T cells to investigate the tolerogenic potential of OM-MOG35–55 for its possible use in MS therapy. To this end, monocytes were differentiated into different DC types in the presence of IL-4+GM-CSF ± dexamethasone (DEXA) ± vitamin D3 (VITD3). At the end of their differentiation, the DCs were loaded with peptides and co-cultured with T cells +IL-2 for 4 antigen presentation cycles. The phenotypes of the DC and T cell populations were analyzed using flow cytometry and the secreted cytokines using flow cytometry or ELISA. On day 8, the monocytes had converted into DCs expressing the typical markers of mature or immature phenotypes. Co-culture of T cells with all DC types for 4 antigen presentation cycles resulted in an increase in memory CD4+ T cells compared to memory CD8+ T cells and a suppressive shift in secreted cytokines, mainly due to increased TGF-β1 levels. The best tolerogenic effect was obtained when patient CD4+ T cells were co-cultured with VITD3-DCs presenting OM-MOG35–55, resulting in the highest levels of CD4+PD-1+ T cells and CD4+CD25+Foxp3+ Τ cells. In conclusion, the tolerance induction protocols presented in this work demonstrate that OM-MOG35–55 could form the basis for the development of personalized therapeutic vaccines or immunomodulatory treatments for MS.

show abstract

General Principles of Immunotherapy in Neurological Diseases

Rommer,

Hecker,

Zrzavy

et al. 2024

Neuroimmune Diseases

View full text Add to dashboard Cite

Current knowledge on multiple sclerosis pathophysiology, disability progression assessment and treatment options, and the role of autologous hematopoietic stem cell transplantation

Cited by 3 publications

References 187 publications

RNA 5ʹ terminal nucleotide determines the strength of the RIG-I/IFN signaling pathway

RNA 5ʹ terminal nucleotide determines the strength of the RIG-I/IFN signaling pathway

Myelin Oligodendrocyte Glycoprotein (MOG)35–55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis

General Principles of Immunotherapy in Neurological Diseases

Contact Info

Product

Resources

About