Project Description

Type 1 diabetes (T1D) is a chronic inflammatory disease, which affects nearly 1.6 million Americans. In the classical view of T1D, pancreatic beta cells are mistakenly destroyed by immune systems. While the classical view of T1D still holds, further evidence shows that beta cells play a vital role in T1D development and are not simply passively destroyed. Our laboratory illustrated that a specific type of beta cells, aging beta cells, accumulate with the progression of T1D in both rodents and humans.

Furthermore, the elimination of these beta cells halted the immune-mediated beta-cell destruction and prevents T1D in the mouse model. Of note, aging cells can normally be recognized and removed by the immune system. In the T1D model, however, patrolling immune cells fail to recognize and eliminate this type of beta-cell, causing them to accumulate and spread in the pancreas.

The failure of immune cells in T1D development raises a couple of questions: how do the aging β-cells evade immune removal in T1D? Do these cells play a role in wider immune regulation with T1D?

Aging, or senescent, cell communication depends on the release of senescence-associated secretory phenotypes (SASPs), which affect the function of bystander cells. Extracellular vesicles (EVs) are a group of SASPs which carry and transfer various proteins, RNA, and lipids that derived from parental cells. EVs function as carriers of signals that regulate the immune response in T1D.

In this context, senescent beta cells might regulate the immune response via the release of EVs. The goal of this project is to determine the role of EVs that are secreted from senescent beta cells in the ultimate development of T1D. These findings will then lead to a comprehensive understanding of why these cells accumulate with T1D development.

To determine the role of EVs secreted from senescent beta cells, we will first identify the specific antigen-presenting molecules carried by EVs derived from the senescent beta cells, with comparison to those carried by normal EVs. Second, we will examine whether EVs that derived from senescent beta cells can be taken up by the typical antigen-presenting cells. Third, we will evaluate whether EVs that derived from senescent beta cells can affect native T cell activation, which ultimately plays a role in pancreatic beta cells destruction.

In addition to the mouse model, we will use pancreatic beta cells from human donors. Therefore, our findings are more relative to T1D in humans and could be more applicable for therapeutic purposes.

To view Dr. Wang’s video, click HERE.