Regulatory B Cells Promote Remyelination in a Mouse Model of Multiple Sclerosis: Defining the Role of Bregs-Responsive CNS-Resident T Cells in Oligodendrogenesis
Abstract
This proposal responds to the FY21 MSRP Investigator-Initiated Research Award Focus Area Central Nervous System Regenerative Potential in Demyelinating Conditions through cell-based therapies. Our objective is to understand the way oligodendrocytes progenitor cells (OPC) can be recruited and activated to the site of myelin lesions in the spinal cord. In multiple sclerosis (MS) patients, central nervous system damage from demyelination occurs with aging and disease course. There are several drugs approved by the U.S. Food and Drug Administration to treat the relapsing form of the disease. However, none of these therapies cure the disease nor are they able to repair the damage already done, making MS a major cause of non-traumatic progressive disability in young people. Just in the United States, it has been estimated that nearly 1 million people over the age of 18 live with the disease, including some active military personnel and many Veterans. Our team has discovered, using a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), that the transfusion of manufactured regulatory B cells (a naturally extremely rare population of cells) is able to ameliorate, cure, and sustain the durable remission of the disease. We recently showed that OPC are activated and differentiate into pre- and myelinating oligodendrocytes, which results in neo-oligodendrogenesis and secondarily remyelination. This laboratory study will provide critical new insight on how regulatory B cells can induce remyelination by normalizing the central nervous system immune environment and possibly will speed up the translation of this cell-based therapy into clinical trials in people suffering with multiple sclerosis. From a clinical standpoint, a simple blood collection will provide the starting material for the cell-based therapy. Isolated B cells will be induced in vitro to a B cell regulatory phenotype that can then be reinfused into the patients. Distinct from traditional immune suppressive therapies that attempt to deplete or counteract inflammation, one can envision that regulatory B cell therapy will be used to normalize the homeostasis of the central nervous system and induce regeneration of myelin sheaths along the axons.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210832
Entities
People
- Jacques Galipeau
Organizations
- United States Army
- University of Wisconsin–Madison