Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strate- gies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System

Abstract: The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by pro-fessional 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 autoim-mune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is im-portant to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to ex-plore 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 in-duced 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 benefit