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
The Goal of this proposal is to address the mechanism of remyelination of the central nervous system (CNS) arising from regulatory B cells (Bregs) adoptive cell therapy, in a mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Our analytical focus is defining functional Bregs interaction with T cells and downstream activation/maturation of oligodendrocytes progenitor cells (OPC). In detail we are planning to 1) define key factors secreted by Bregs essential for the modulation of T cells in the remyelination process post Bregs adoptive transfer, and 2) define the nature of IL-10 producing T cells and 3) key secreted factor in the CNS-like IL-10 for the activation/maturation of OPC in the remyelination process observed post-Bregs adoptive transfer. During the past year, based on the timelines indicated in the SOW we first obtained a new regulatory IACUC protocol that allowed ACCURO approval. We were then able to work on the role of IL-27 and IL-10 on the regenerative polarization of T cells in the periphery. IL-27 showed to be an essential Bregs secreted cytokine for the peripheral polarization of T cells post Bregs adoptive transfer in EAE mice. IL-10 competency of encephalitogenic T cells does not have a major effect post Bregs adoptive transfer as indicated by significative resolution of EAE symptoms post wild type EAE adoptive transfer. This will allow us to directly test the function of Bregs secreted factors in the remyelination and regenerative properties observed post adoptive transfer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1216084
Entities
People
- Andrea Pennati
- Catigan Hedican
- Jacques Galipeau
- Shala Yuan
- Xingyi Tang
Organizations
- University of Wisconsin–Madison