Dextran Sulfate, Beta Cell Preservation, and Immune Regulation in Type 1 Diabetes
Abstract
In Type 1 diabetes (T1D), therapies focused on decreasing T cell activation to preserve functional cells are a priority for the treatment of the disease. We have found that the sulfated polysaccharide dextran sulfate(DS) reduces mouse interferon-+CD4+ and CD8+ T cells, increases mouse FoxP3+ cells (Tregs), preserves Beta cells and reverses T1D in mice (Lu et al. Diabetes, 2020, PMID: 32381645). In the DoD funded project (only Specific Aim 3 of the original application was funded), we studied the immunomodulatory effects of DS in human immune cells. Using hPBMCs from healthy individuals and flow cytometry and CyTOF techniques we have found that DS alters phenotypic markers of CD8+ and macrophage-like cells [subaim (sa) 3.1]; DS reduces expression of dendritic cells (DCs) co-stimulatory molecules, leading to enhanced Treg differentiation and reduced proliferation ofactivated T-cells (sa 3.2); DS does not have direct effects on T-cell activation or differentiation in whole PBMCs, isolated T-cells, or nave CD4+-targeted differentiation with different stimulatory methods (sa 3.3); and these changes might be mediated by HGF/c-Met signaling pathway as shown in mouse myeloid cells (sa 3.4), although this requires further studies in hPBMCs. A manuscript with these observations is in preparation. In conclusion, DS induces a more tolerogenic phenotype in activated hPBMCs from healthy donors. Next, we will test whether similar DS-induced pro-tolerogenic effects occur in hPBMCs from Type 1 diabetic individuals.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2020
- Accession Number
- AD1141229
Entities
People
- Adolfo Garcia-Ocaña
- Dirk Homann
Organizations
- Icahn School of Medicine at Mount Sinai