Accession Number:

AD1094805

Title:

Dextran Sulfate, Beta Cell Preservation, and Immune Regulation in Type 1 Diabetes

Descriptive Note:

Technical Report,01 Aug 2018,31 Jul 2019

Corporate Author:

Icahn School of Medicine at Mount Sinai New York United States

Personal Author(s):

Report Date:

2019-08-01

Pagination or Media Count:

15.0

Abstract:

Type 1 diabetes T1D, with an increasing incidence 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 beta cell destruction. Autoreactive T cells acquire an effector inflammatory phenotype due to co-stimulatory signals leading to tissue invasion and beta cell destruction. Therapies focused on decreasing T cell activation to preserve functional beta 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 beta cells, but the therapeutic potential in humans is unknown. During the second year of the award, we have found that DS reduces human CD4 T cell activation decrease in interferon-gamma CD4 T cells when stimulated with anti-CD3CD28. This correlates with changes in phenotypic markers of antigen presenting capacity in LPS-stimulated APC populations. Ongoing experiments are testing DS effects in human PBMCs from T1D donors.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE