Estefania Quesada-Masachs, M.D. Ph.D

What if a person’s insulin-producing beta cells are orchestrating their own demise?

Type 1 diabetes (T1D), an autoimmune disease that usually affects young people, is on the rise worldwide, and there is no cure to date. We still do not completely understand the underlying processes that drive the dysfunction and destruction of insulin-producing β cells in the pancreas leading to a lifelong dependency on insulin injections. It is key that we understand whether this disease is primarily triggered by the β cell itself or by the immune system to offer better therapeutic options.

One of the questions that has arisen is whether β cells are orchestrating their own demise by causing a direct response in the immune cells around them. Several discoveries have suggested this notion. Recently, we have demonstrated that β cells can express HLA class II in patients with T1D. HLA class II is a molecule that can be used by our own cells to “give orders” to our immune system. When an immune cell contacts HLA class II it responds to proteins that otherwise would probably be ignored. Whether β cells can express HLA class II in T1D has been a controversial topic for decades, and we have just settled this controversy recently. I have demonstrated that even healthy β cells in isolated human islets can express HLA class II when they are stressed. Based on these advancements, my hypothesis is that β cells can affect the behavior of immune T cells around them.

As part of an ongoing collaboration, I will obtain human pancreatic islets (from City of Hope), and human islet microtissues using an innovative 3D platform (from InSphero). T cells from compatible donors will be cultured with these islets. I will determine changes in islet function and structure and the magnitude of T cell infiltration under different conditions, using state-of-the art microscopy systems. Subsequent experiments will seek to uncover the effect of those interactions on the immune T cells.

It is key to understand whether β cells influence the responses of T cells around them. This finding will be of major importance to our understanding of T1D pathogenesis, and it will drastically impact future treatment approaches.

SPARKing Impact: Determining the mechanism behind the destruction of insulin-producing cells has the potential to radically change the future approach to novel treatments for type 1 diabetes.