Dextran Sulfate, Beta Cell Preservation, and Immune Regulation in Type 1 Diabetes
Abstract
Type 1 diabetes (T1D), with an incidence that has been increasing by 2-5% worldwide over the past few years, poses a considerable challenge to afflicted individuals, to the development of effective prevention and treatment regimens, and to public health initiatives at large. In T1D, self-tolerance is lost leading to the destruction of insulin-producing cells. Autoreactive T cells acquire an effector inflammatory phenotype due to costimulatory signals leading to tissue invasion and insulin-producing cell destruction. Therapies focused on gaining immune tolerance to preserve functional insulin-producing cells are a priority for the treatment of the disease. We found that the semi-synthetic proteoglycan dextran sulfate (DS) decreases diabetes incidence in mice and preserves insulin-producing cells. During the first year of the award, we have determined that DS treatment induces a spectrum of phenotypic changes consistent with a tolerogenic modulation of human APC and/or T cell. Alterations in CXCR3, CD62L, CD25, CD38 in T cells and CD123, PDL1 and HLA-DR in APCs are observed and their importance in DS effects will be assessed next year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1056822
Entities
People
- Adolfo Garcia-Ocaña
- Dirk Homman
Organizations
- Icahn School of Medicine at Mount Sinai