Role of the Innate Immune System in Autoimmune Inflammatory Demyelination
Abstract:Considerable research has been devoted to the role of the adaptive immune system in the pathogenesis of autoimmune inflammatory demyelination (AID). AID is thought to occur spontaneously in patients with multiple sclerosis (MS), a common cause of neurological disability. AID is also observed in the best characterized animal model of MS, experimental autoimmune encephalomyelitis (EAE). The adaptive immune system recognizes and responds to antigens via highly specific T-cell receptors. Myelin-reactive T-cells may initiate pathological immune responses that lead to central nervous system damage in MS and EAE. By contrast, the innate immune system recognizes evolutionarily conserved structures that are common to invading pathogens with high efficiency for rapid recognition and elimination of viruses, bacteria, and fungi. This recognition is mediated by pattern-recognition receptors such as Toll-like receptors (TLRs) expressed on cells of the innate immune system (dendritic cells and CNS-resident cells, such as microglia) that have the potential to activate autoimmune responses by inducing the production of inflammatory cytokines and chemokines. Conversely, the innate immune system can also regulate autoimmune inflammation by inducing the production of immunoregulatory molecules such as type I interferons, which are currently used in the treatment of MS. We review the evidence that TLRs can exacerbate or regulate AID and discuss the therapeutic potential of targeting either process.
Document Type: Research Article
Affiliations: Division of Clinical Neurology, Nottingham University Hospitals, B31 Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Publication date: May 1, 2008
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