Immune Promotion of Remyelination

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Autoimmune responses directed against the central nervous system (CNS) have generally been considered pathogenic in nature. While there are several well understood conditions in which this is the case, there is also a growing body of experimental evidence that both the cellular and humoral immune responses can promote tissue repair following CNS injury and disease. Our laboratory has used various mouse models of demyelinating disease (Theiler's virus, EAE, lysolecithin) to characterize a class of polyreactive IgM autoantibodies that react with oligodendrocyte surface antigens and that promote myelin repair. The purpose of this grant is to evaluate the mechanism by which mouse and human monoclonal antibodies function to promote remyelination via a direct effect on glial cells. Our specific aims are to: 1. Characterize antibody-induced changes in the local organization of the plasma membrane of oligodendroglia, and to identify the membrane microdomain relevant to antibody-induced signaling. 2. Characterize antibody-induced signaling cascades and identify the second messenger systems relevant to the induction of transcriptional changes involved in oligodendroglial survival, proliferation, and differentiation. 3. Use the lysolecithin model to assess the in vivo effects of treatment with pharmacologic agents (as identified in Aims 1 & 2) on the CNS response to remyelination promoting antibodies. Our findings are expected to provide new insights into the enhancement of remyelination in diseases such as multiple sclerosis. [unreadable] [unreadable]