Update on inflammation, neurodegeneration, and immunoregulation in multiple sclerosis: therapeutic implications.
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system of uncertain etiology. There is consensus that a dysregulated immune system plays a critical role in the pathogenesis of MS; therefore, we aim to summarize current hypotheses concerning the complex cellular and molecular interactions involved in the immunopathology of MS. Although CD4+ T lymphocytes have long been implicated in the immunopathology of MS, the role of other T-cell subtypes has been recognized. CD4+ and CD8+ cells have been isolated from different locations within MS lesions and gamma/delta T cells have been isolated from early MS lesions. The prevalent dogma has been that CD4+ TH1 cells release cytokines and mediators of inflammation that may cause tissue damage, although CD4+ TH2 cells may be involved in modulation of these effects. Recent evidence, however, suggests that additional T-cell subsets play a prominent role in MS immunopathology: TH17 cells, CD8+ effector T cells, and CD4+CD25+ regulatory T cells. In addition, laboratory and clinical data are accumulating on the prominent role of B lymphocytes and antigen-presenting cells in MS pathogenesis. On the basis of these observations, new therapeutic approaches for MS will need to focus on resetting multiple components of the immune system.
Bennett
Jeffrey L
JL
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Jeffrey.bennett@uchsc.edu
Stüve
Olaf
O
D000818:Animals; D006801:Humans; D055633:Immune System Phenomena / Q000187:drug effects / Q000502:physiology; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000628:therapy; D009103:Multiple Sclerosis / Q000150:complications / Q000276:immunology / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000150:complications / Q000276:immunology / Q000628:therapy
D007155:Immunologic Factors