Death ligands and autoimmune demyelination.
Death ligands induce apoptosis, which is a cell suicide program leading mainly to selective elimination of an organism's useless cells. Importantly, the dying cell is an active participant in its own demise ("cellular suicide"). Under physiological conditions, apoptosis is most often found during normal cell turnover and tissue homeostasis, embryogenesis, induction and maintenance of immune tolerance, development of the nervous system, and endocrine-dependent tissue atrophy. However, apoptotic processes have also been suggested to contribute to the pathology of the autoimmune demyelinating disease multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis. Here, apoptosis plays a double role. On one hand, impaired apoptosis may result in increased numbers or persistence of activated myelinspecific T cells. On the other hand, local tissue damage involves apoptosis of oligodendrocytes and neurons, leading to the clinical symptoms. In this article, an overview is given of the current knowledge of the roles of apoptosis-mediating and immune regulatory death ligands of the tumor necrosis factor (TNF) family (TNF, lymphotoxin-beta, OX40L [CD134L], CD154 [CD40L], CD95L, CD70 [CD27L], CD153 [CD30L], 4-1BBL [CD137L], TRAIL, TWEAK, BAFF, GITRL) in the pathogenesis of MS and of their implications for related therapeutic strategies.
Aktas
Orhan
O
Institute of Neuroimmunology, Clinical and Experimental Neuroimmunology, Charité--Universitätsmedizin Berlin, Germany.
Prozorovski
Timour
T
Zipp
Frauke
F
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D014409:Tumor Necrosis Factor-alpha