Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis.
The interaction between the immune and nervous systems can be both detrimental and beneficial. Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune demyelination that histologically and clinically mimics multiple sclerosis (MS). Myelin-reactive T cells produce and release brain-derived neurotrophic factor (BDNF) directly in the central nervous system, which stimulates tissue repair after traumatic injury. In EAE and MS, T cells in the vicinity of actively demyelinating lesions express BDNF, suggesting a neuroinflammatory reaction that is designed to limit brain damage and contribute to the repair process. Despite some evidence supporting MS therapies that enhance BDNF production by immune cells, no published reports have actually demonstrated that increased BDNF production can substantially ameliorate the clinical symptoms of MS. BDNF binds to a small subset of peripheral T cells that express TrkB, which is the BDNF receptor. This binding confers a partial resistance to apoptosis upon T cell activation, which could underlie the chronic nature of the inflammatory process. Here we will review the main aspects of BDNF and TrkB receptor involvement in neuroprotective autoimmunity in both EAE and MS. We will also discuss the latest findings with respect to the role of the BDNF/TrkB axis in regulating the survival of autoreactive T cells, with a focus on potential selectively immunomodulating strategies that may favor neuroprotection in MS.
De Santi
Lorenzo
L
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy. lorenzo.desanti@centroneurolesi.it
Annunziata
Pasquale
P
Sessa
Edoardo
E
Bramanti
Placido
P
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D019610:Cytoprotection / Q000276:immunology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D009416:Nerve Regeneration / Q000276:immunology; D020813:Receptor, trkB / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D007155:Immunologic Factors; D020813:Receptor, trkB