Objective
Our goal is to identify the subtypes of myeloid cells in human islets and determine which subtype of myeloid cells interacts with and stimulates the T cells in the islets. We also aim to identify therapeutically targetable proteins on islet myeloid cells that make T cells more dangerous during type 1 diabetes.
Background Rationale
Myeloid cells are the most abundant immune cell type in the pancreatic islets of non-diabetic people and many type 1 diabetic people. Studies in mouse models have shown that myeloid cells have many roles in type 1 diabetes. They can stimulate the T cells that cause type 1 diabetes to make them more dangerous or they can protect the pancreatic islets by suppressing the dangerous T cells. The ability of islet myeloid cells to control type 1 diabetes causing T cells makes them an attractive therapeutic target. However, the myeloid cells in the islets are a complex population of cells that are made up of subtypes that likely have different effects on the T cells. The myeloid cells in human islets are severely understudied, so we do not yet have information about the subtypes of myeloid cells in human islets. In order to therapeutically target the islet myeloid cells in type 1 diabetes, we first must identify the myeloid cell populations that stimulate the disease-causing T cells and those that suppress them.
Description of Project
Myeloid cells are the most abundant immune cell type in the pancreatic islets of non-diabetic people and many type 1 diabetic people. Studies in mouse models have shown that myeloid cells have many roles in type 1 diabetes. They can stimulate the T cells that cause type 1 diabetes to make them more dangerous or they can protect the pancreatic islets by suppressing the dangerous T cells. The ability of islet myeloid cells to control type 1 diabetes causing T cells makes them an attractive therapeutic target. However, the myeloid cells in the islets are a complex population of cells that are made up of subtypes that likely have different effects on the T cells. The myeloid cells in human islets are severely understudied, so we do not yet have information about the subtypes of myeloid cells in human islets. Thus, our goal is to identify the subtypes of myeloid cells in human islet and determine which subtype of myeloid cells interacts with and stimulates the T cells in the islets. We also aim to identify therapeutically targetable proteins on the islet myeloid cells that make T cells more dangerous during type 1 diabetes.
Anticipated Outcome
Our analysis will represent the most in-depth description and analysis of myeloid cell populations and their interactions with T cells ever reported in human non-diabetic and T1D islets. We anticipate that we will identify islet myeloid cell populations that are the dominant stimulators of type 1 diabetes causing T cells and might identify myeloid populations that are responsible for protecting the pancreatic islets.
Relevance to T1D
To prevent or treat type 1 diabetes, we need to stop the disease-causing T cells from destroying the beta cells in the pancreatic islets. The ability of islet myeloid cells to control type 1 diabetes causing T cells makes them an attractive therapeutic target. However, the myeloid cells in human islets are severely understudied, so we do not yet have information about the subtypes of myeloid cells in human islets. Our goal is to identify the subtypes of myeloid cells in human islet and determine which subtype of myeloid cells interacts with and stimulates the T cells in the islets, to enable us to therapeutically target those cells to treat type 1 diabetes. We also aim to identify therapeutically targetable proteins on pathogenic islet myeloid cells.