TY - JOUR
T1 - Role of the CD200-CD200R Axis During Homeostasis and Neuroinflammation
AU - Manich, Gemma
AU - Recasens, Mireia
AU - Valente, Tony
AU - Almolda, Beatriz
AU - González, Berta
AU - Castellano, Bernardo
PY - 2019/5/1
Y1 - 2019/5/1
N2 - © 2018 Microglia are considered to be the resident macrophages of the CNS and main effector of immune brain function. Due to their essential role in the regulation of neuroinflammatory response, microglia constitute an important target for neurological diseases, such as multiple sclerosis, Alzheimer's or Parkinson's disease. The communication between neurons and microglia contributes to a proper maintenance of homeostasis in the CNS. Research developed in the last decade has demonstrated that this interaction is mediated by “Off-signals” – molecules exerting immune inhibition – and “On signals” – molecules triggering immune activation. Among “Off signals”, molecular pair CD200 and its CD200R receptor, expressed mainly in the membrane of neurons and microglia, respectively, have centered our attention due to its unexplored and powerful immunoregulatory functions. In this review, we will offer an updated global view of the CD200-CD200R role in the microglia-neuron crosstalk during homeostasis and neuroinflammation. Specifically, the effects of CD200-CD200R in the inhibition of pro-inflammatory microglial activation will be explained, and their involvement in other functions such as homeostasis preservation, tissue repair, and brain aging, among others, will be pointed out. In addition, we will depict the effects of CD200-CD200R uncoupling in the etiopathogenesis of autoimmune and neurodegenerative diseases. Finally, we will explore how to translate the scientific evidence of CD200-CD200R interaction into possible clinical therapeutic strategies to tackle neuroinflammatory CNS diseases.
AB - © 2018 Microglia are considered to be the resident macrophages of the CNS and main effector of immune brain function. Due to their essential role in the regulation of neuroinflammatory response, microglia constitute an important target for neurological diseases, such as multiple sclerosis, Alzheimer's or Parkinson's disease. The communication between neurons and microglia contributes to a proper maintenance of homeostasis in the CNS. Research developed in the last decade has demonstrated that this interaction is mediated by “Off-signals” – molecules exerting immune inhibition – and “On signals” – molecules triggering immune activation. Among “Off signals”, molecular pair CD200 and its CD200R receptor, expressed mainly in the membrane of neurons and microglia, respectively, have centered our attention due to its unexplored and powerful immunoregulatory functions. In this review, we will offer an updated global view of the CD200-CD200R role in the microglia-neuron crosstalk during homeostasis and neuroinflammation. Specifically, the effects of CD200-CD200R in the inhibition of pro-inflammatory microglial activation will be explained, and their involvement in other functions such as homeostasis preservation, tissue repair, and brain aging, among others, will be pointed out. In addition, we will depict the effects of CD200-CD200R uncoupling in the etiopathogenesis of autoimmune and neurodegenerative diseases. Finally, we will explore how to translate the scientific evidence of CD200-CD200R interaction into possible clinical therapeutic strategies to tackle neuroinflammatory CNS diseases.
KW - EAE
KW - immunoregulation
KW - microglia-neuron communication
KW - microglial priming
KW - neurodegeneration
KW - off-receptor
U2 - 10.1016/j.neuroscience.2018.10.030
DO - 10.1016/j.neuroscience.2018.10.030
M3 - Review article
C2 - 30367946
SN - 0306-4522
VL - 405
SP - 118
EP - 136
JO - Neuroscience
JF - Neuroscience
ER -