News & Research

    University of Minnesota, Minneapolis, Minnesota

The role of PTPn22, diabetes risk gene, in Type 1 interferon regulation

General Research Subject: Type 1 Diabetes

Focus: Genetics\Type 1 Diabetes, Immunology, Signal Transduction (Non-Insulin Action)\Transgenic Models

Type of Grant: Basic Science

Project Start Date: January 1, 2012

Project End Date: December 31, 2014

Research Description

The cause of Insulin Dependent (Type 1) Diabetes is not known. However, tissue-damaging behavior by cells of the immune system is required for destruction of insulin-producing cells in the pancreas. One subset of immune cells, myeloid cells of the innate immune system, functions as an "early warning system" against infection by viruses. Myeloid produced chemicals that attract other inflammatory cells to the vicinity of the pancreas and that strengthen the tissue-damaging immune response. One such pro-inflammatory chemical is Type I Interferon. Interferon is normally produced in response to virus infection. If too much interferon is produced, however, an unchecked immune response may result. Preliminary data from the Peterson group show that PTPn22, a recently discovered "risk gene" for Diabetes, controls interferon after cells are stimulated with substances that mimic viral infection. The research in this proposal will examine the molecular controls of Type I interferon. Experiments using both human blood samples and genetically-altered mice will be conducted to determine the molecular mechanism whereby PTPn22 governs production of interferons. Results of the research will advance understanding of the relationship between genetic risk for diabetes and the early phase of immune cell tissue damage in the pancreas.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Tissue-damaging behavior by cells of the immune system is required for destruction of insulin-producing cells in the pancreas to cause Insulin Dependent (Type 1) Diabetes (T1D). One subset of immune cells, myeloid cells of the innate immune system, functions as an "early warning system" against infection by viruses. Myeloid cells produce chemicals that attract other inflammatory cells to the vicinity of the pancreas and that strengthen the tissue-damaging immune response. One such pro-inflammatory chemical is Type I Interferon. Interferon is normally produced in response to virus infection. If too much interferon is produced, however, an unchecked immune response might result. Conversely, if too little interferon is produced, overwhelming viral infection can destroy the islets. The research in this proposal will examine the molecular controls of Type I interferon relative to diabetes. PTPn22 is a recently discovered "risk gene" for T1D. Our data shows the surprising finding that PTPn22 controls interferon production by myeloid cells after they are stimulated with viral infection mimics. Experiments using both human blood samples and genetically altered mice will be conducted to determine the molecular mechanism whereby PTPn22 governs production of interferons. Results of the research will advance understanding of the relationship between genetic risk for diabetes and the early phase of tissue damage in the pancreas caused by infection or by myeloid cells. Our goal is to identify new molecular targets to permit prevention or early abortive therapy of T1D.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

The ideal way to treat T1D is to prevent it. Our project will result in better understanding of how infection by viruses and bacteria can lead to death of insulin producing cells. Our goal is to identify new molecular targets to permit prevention or early abortive therapy of T1D. Once the cellular or molecular targets are identified, we can develop specific new prevention methods or apply already existing treatments to reduce the incidence of the disease.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

As a researcher, I have a long-standing interest in defining the disease-causing chain of events at the molecular level. As a physician, I encounter the devastating effects of tissue damage resulting from autoimmune diseases such as T1D every day in clinic. As a cousin of 2 adults who have suffered from T1D and its complications for 35 years, I have an abiding passion to understand and defeat this disease.

In what direction do you see the future of diabetes research going?

Fantastic advances are being made in transplantation and other means of restoring insulin-producing function in people with T1D. However, equally exciting are improvements in the understanding of how infections, immune cells, and pancreatic cells interact both normally and in disease. Basic understanding of these mechanisms will ultimately lead us to a position where loss of insulin-producing function can be prevented in the first place.