Beta Cell-Immune Cell Crosstalk

β-cell endoplasmic reticulum (ER) stress may influence immune cell activation and function in the pancreas through a multitude of mechanisms. For example, ER stress interferes with major histocompatibility complex (MHC) class I protein surface expression and peptide presentation, thus differentially regulating expression of ER- versus cytosol-derived peptide. During cellular stress, ER chaperones that are typically retained in the ER are translocated to the cell surface upon stress and act as an “eat me” signal. These proteins can be released from chronically stressed and dying cells and activate the immune system. Moreover, in addition to the immune effectors, β-cells themselves secrete chemokines during insulitis and contribute to the early steps of T cell activation and inflammation. Finally, ER stress in one cell population can influence neighboring cells. Through a cell non-autonomous mechanism β-cells can transmit their ER stress to immune cells.

Our lab is interested in answering the following questions:

How do stressed β-cells communicate with immune cells?

Can mitigation of stress in β-cells alter the diabetogenic activity of immune cells?