June 30, 2022

DICAM Contributes to Autoimmune Neuroinflammation by Promoting Immune Cell Migration into the Central Nervous System

The brain is not easily accessible to cells of the immune system as it is surrounded by a relatively impenetrable wall of cells called the blood-brain barrier. However, in multiple sclerosis (MS), a large number of immune cells are able to cross this barrier and drive inflammation in the central nervous system (CNS), leading to the formation of brain lesions. In a recent publication, Dr. Alexandre Prat and his research team at the Centre de Recherche du CHUM describe the role of a protein, called DICAM, in regulating immune cell movement into the CNS.

The study showed that DICAM is found in high levels in MS brain lesions, as well as in people with active relapsing-remitting MS, secondary progressive and primary progressive MS. DICAM is also present in immune cells, specifically T helper 17 cells (TH17), a type of white blood cells that are a leading cause of inflammation in the CNS. Data from the study revealed that DICAM mediates the migration of TH17 cells across the blood-brain barrier and into the CNS. In mice with relapsing-remitting and progressive MS-like disease (i.e. experimental autoimmune encephalomyelitis or EAE mice), the researchers demonstrated that blocking DICAM with a monoclonal antibody reduced TH17 migration across the blood-brain barrier and improved the clinical symptoms of EAE mice (i.e., reduced disease severity, relapses and progression; improved remission and recovery). Overall, this work showed that blocking the activity of DICAM in the mouse model of MS, reduced the presence of inflammation causing immune cells in the CNS and reduced disease severity.

These findings suggest that pharmacologically targeting DICAM is a potentially promising therapeutic strategy to selectively suppress the migration of disease-inducing immune cells into the CNS for people with relapsing-remitting and progressive forms of MS. Future studies will need to evaluate potential health risks of blocking DICAM activity in humans and to determine whether its clinical efficacy is comparable to other available monoclonal antibodies such as natalizumab.

This study was led by Dr. Marc Charabati and Camille Grasmuck, and was published in Science Translational Medicinelink. For more information about the research, click here.