Immunopathogenesis of Multiple Sclerosis: Molecular and Cellular Mechanisms and New Immunotherapeutic Approaches Publisher Pubmed



Aliyu M^{1, 2} ; Zohora FT³ ; Ceylan A⁴ ; Hossain F³ ; Yazdani R⁵ ; Azizi G^{5, 6} Show Affiliations
Source: Immunopharmacology and Immunotoxicology Published:2024

Abstract

Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of European descent. The interplay between environmental factors and genetic predisposition plays a crucial role in MS etiopathogenesis. Methods: We search recent relevant literature on reputable databases, which include, PubMed, Embase, Web of Science, Scopus, ScienceGirect using the following keywords: multiple sclerosis, pathogenesis, autoimmunity, demyelination, therapy, immunotherapy. Results: Various animal models have been utilized to study MS etiopathogenesis and therapeutics. Autoreative T cells within the CNS recruit myeloid cells through chemokine expression, leading to the secretion of inflammatory cytokines driving the MS pathogenesis, resulting in demyelination, gliosis, and axonal loss. Key players include T cell lymphocytes (CD4+ and CD8+), microbiota B cells, and neutrophils. Signaling dysregulation in inflammation pathways and the immunogenetic basis of MS are essential considerations. The pathogenesis of MS involves demyelination, gliosis, and axonal loss driven by inflammatory cytokines. While T cells are traditionally recognized as central to MS, evidence suggests a significant role for B cells and neutrophils. High neutrophil-to-lymphocyte ratios correlate with MS severity, indicating their contribution to disease progression. Dysregulated signaling pathways further exacerbate MS progression. Conclusion: MS remains incurable, but disease-modifying therapies, monoclonal antibodies, and immunomodulatory drugs offer hope for patients. Ongoing research into the immunogenetics and immunoregulatory roles of gut microbiota continues to shed light on potential therapeutic avenues. Understanding the complex interplay between genetic predisposition, environmental factors, and immune dysregulation is critical for developing effective treatments for MS. © 2024 Informa UK Limited, trading as Taylor & Francis Group.