Title:Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System
Volume: 20
Issue: 29
Author(s): Miriam Hernangomez, Francisco J. Carrillo-Salinas, Miriam Mecha, Fernando Correa, Leyre Mestre, Frida Loria, Ana Feliu, Fabian Docagne and Carmen Guaza
Affiliation:
Keywords:
Neuroinflammation, microglia, neurons, neuroimmunoregulatory molecules, CD200, CD200R, multiple sclerosis, aging brain,
Alzheimer’s disease, cannabinoids.
Abstract: The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional
phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However,
any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune
disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important
to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore
novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement
regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence
of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause
injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the
pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced
demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce
our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits
caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain.
