Diabetes and other autoimmune endocrine diseases

No Preference

Jurkats and Type 1 Diabetes: Tcr and Receptor for Advanced Glycation Endproducts Signaling

Thursday, June 15
5:45 PM - 7:00 PM

The receptor for advanced glycation endproducts (RAGE) may be found in adaptive immune cells but its role is not understood. Patients with type 1 diabetes (T1D) express increased levels of intracellular RAGE in T cells, compared to healthy controls, as do euglycemic at-risk relatives who progress to disease. We studied gene expression by nanostring in T cells from type 1 diabetics and found differences in pathways utilized by RAGE+ versus RAGE- T cells including those affecting apoptosis and survival via TNFs/NF-κB/Bcl-2 proteins, IL-12-induced IFN-γ production, and PDGF signaling through STATs and NF-κB proteins.


We studied RAGE signaling in Jurkat cells. We silenced intracellular RAGE with pooled siRNAs causing a 75% reduction in RAGE by flow cytometry FITC mean fluorescence index. Using knockdowns, we found T cell receptor (TCR) signaling interference.  Western blots of RAGE siRNA transfected Jurkats showed decreased baseline levels of Zap70. There was decreased signal amplitude of phosphorylated Erk 1/2 with RAGE siRNA.  The addition of high mobility group box 1 protein (HMGB1), a known RAGE ligand, increased the amplitude of phosphorylated Erk 1/2 signal in submaximally stimulated Jurkats transfected with negative control siRNA but not with RAGE silencing. RAGE siRNA did not affect CD3 surface expression.


RAGE stimulation may enhance TCR signal in T cells. Through the release of multiple ligands during inflammation this mechanisms may facilitate survival and activation of T cells.

James C. Reed

Howard Hughes Medical Institute, Yale School of Medicine

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    Paula Preston-Hurlburt

    Yale University

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      Songyan Deng

      Yale University

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        Sean Durning

        Yale School of Medicine, AbbieVie

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          Kevan Herold

          Professor of Immunology
          Department of Immunobiology and Internal Medicine, Yale University

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