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

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[Technical Report, Final Report]

Corporate Author:

Icahn School of Medicine at Mount Sinai

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In Type 1 diabetes T1D, therapies focused on decreasing T cell activation to preserve functional Beta cells are a priority for the treatment of the disease. We have found that the sulfated polysaccharide dextran sulfateDS 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 of activated 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 HGFc-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 similarDS-induced pro-tolerogenic effects occur in hPBMCs from Type 1 diabetic individuals.

Subject Categories:

  • Medicine and Medical Research
  • Medicine and Medical Research

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[A, Approved For Public Release]