Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain.
Apoptosis mediated by members of the tumor necrosis factor (TNF)-nerve growth factor superfamily plays a crucial role in the interaction of the nervous and the immune system. On the one hand, it is involved in the defense mechanisms of the brain, the immune privilege. On the other hand, it is involved in the induction of glial-neuronal cell death in neuroinflammatory diseases. Here, we show that in contrast to the other known death ligands, TNF-related apoptosis-inducing ligand (TRAIL) is not constitutively expressed in the human brain, whereas both apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons, astrocytes, and oligodendrocytes. Thus, the brain differs from other immune-privileged organs, such as the placenta, with the TRAIL receptor-TRAIL system not being part of the immune privilege of the brain. Conversely, this death receptor-ligand system might well play an important role in T cell-mediated autoimmune diseases of the CNS such as multiple sclerosis.
Dörr
Jan
J
Department of Neurology, Division of Neuroimmunology, Charité Neuroscience Research Center, 10098 Berlin, Germany.
Bechmann
Ingo
I
Waiczies
Sonia
S
Aktas
Orhan
O
Walczak
Henning
H
Krammer
Peter H
PH
Nitsch
Robert
R
Zipp
Frauke
F
D000918:Antibody Specificity; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002460:Cell Line; D004827:Epilepsy / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D010920:Placenta / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000172:deficiency* / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha