TY - JOUR
T1 - Type 1 narcolepsy
T2 - a CD8(+) T cell-mediated disease?
AU - Degn, Matilda
AU - Kornum, Birgitte Rahbek
N1 - © 2015 New York Academy of Sciences.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune attack, and this is supported by evidence of both environmental and genetic factors pointing toward an involvement of the immune system. However, definitive proof of an autoimmune etiology is still missing. Several different immune-mediated disorders targeting neurons are known, and many of these are believed to be caused by autoreactive CD8(+) T cells. In this paper, we review the current knowledge on CD8(+) T cell-mediated neuronal damage on the basis of our understanding of other autoimmune disorders and experimental studies. We identify major histocompatibility complex class I presentation of autoantigens on neurons as a possible mechanism in the development of the disease, and propose T cell-mediated pathogenesis, with cytotoxic CD8(+) T cells targeting the hypocretinergic neurons, as a central element.
AB - Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune attack, and this is supported by evidence of both environmental and genetic factors pointing toward an involvement of the immune system. However, definitive proof of an autoimmune etiology is still missing. Several different immune-mediated disorders targeting neurons are known, and many of these are believed to be caused by autoreactive CD8(+) T cells. In this paper, we review the current knowledge on CD8(+) T cell-mediated neuronal damage on the basis of our understanding of other autoimmune disorders and experimental studies. We identify major histocompatibility complex class I presentation of autoantigens on neurons as a possible mechanism in the development of the disease, and propose T cell-mediated pathogenesis, with cytotoxic CD8(+) T cells targeting the hypocretinergic neurons, as a central element.
KW - Autoantibodies/immunology
KW - Autoimmune Diseases/immunology
KW - Autoimmunity/immunology
KW - Brain/immunology
KW - CD8-Positive T-Lymphocytes/immunology
KW - Histocompatibility Antigens Class I/immunology
KW - Humans
KW - Inflammation/immunology
KW - Narcolepsy/immunology
KW - Nervous System Diseases/immunology
KW - Orexins/deficiency
U2 - 10.1111/nyas.12793
DO - 10.1111/nyas.12793
M3 - Review
C2 - 26096261
SN - 0077-8923
VL - 1351
SP - 80
EP - 88
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -