title: Advances in the immunopathogenesis of multiple sclerosis.
abstract: OBJECTIVE
  Recent studies indicate a role for immune dysregulation in the pathogenesis of multiple sclerosis, an inflammatory demyelinating and degenerative disease of the central nervous system. This review addresses the current mechanisms of immune dysregulation in the development of multiple sclerosis, including the impact of environmental risk factors on immunity in both multiple sclerosis and its animal models.
  
  
  RESULTS
  CD4 T-helper (Th) cells have long been implicated as the main drivers of pathogenesis of multiple sclerosis. However, current studies indicate that multiple sclerosis is largely a heterogeneous disease process, which involves both innate and adaptive immune-mediated inflammatory mechanisms that ultimately contribute to demyelination and neurodegeneration. Therefore, B cells, CD8 T cells, and microglia/macrophages can also play an important role in the immunopathogenesis of multiple sclerosis apart from proinflammatory CD4 Th1/Th17 cell subsets. Furthermore, increasing evidence indicates that environmental risk factors, such as Vitamin D deficiency, Epstein-Barr virus, smoking, Western diet, and the commensal microbiota, influence the development of multiple sclerosis through interactions with genetic variants of multiple sclerosis, thus leading to the dysregulation of immune responses.
  
  
  CONCLUSIONS
  A better understanding of immune-mediated mechanisms in the pathogenesis of multiple sclerosis and the contribution of environmental risk factors toward the development of multiple sclerosis will help further improve therapeutic approaches to prevent disease progression.
authors.affiliation: Department of Neurology, Rutgers-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Yadav
authors.forename: John E
authors.initials: JE
authors.lastname: Mindur
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ito
authors.forename: Suhayl
authors.initials: S
authors.lastname: Dhib-Jalbut
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000473:pathology* / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines