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Zheng, Guoxing
Obesity-induced autoimmune T cells

General Research Subject: Obesity
Focus: Immunology
Type of Grant: Innovation
Project Start Date: July 1, 2011
Project End Date: June 30, 2013
Research Description
Obesity is a major risk factor for type 2 diabetes. The connection between obesity and diabetes is due to obesity-associated chronic low-grade inflammation of fat tissue, which interferes with the body's normal production of, and response to, insulin. To understand how obesity induces inflammation, it is hypothesized that obesity may activate T cells that in turn function as proinflammatory mediators. Our hypothesis is based on our recent detection in obese, but not lean, mice of a T cell population that specifically reacts to a component of the fat cell called heat shock protein 60. In this grant application, it is proposed to examine the role of this cell population in fat tissue inflammation. This study will involve isolating the heat shock protein 60-reactive T cells from obese mice, characterizing their cellular features, and analyzing their in vitro and in vivo functions with regard to fat cell inflammation, macrophage infiltration, and insulin resistance. The proposed study may reveal an important immune mechanism for obesity-induced inflammation and enable T cell-targeted approaches for prevention and treatment of type 2 diabetes.
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?
This project focuses on a major risk factor for type 2 diabetes: obesity. Specifically, it aims to understand how obesity can lead to diabetes by investigating the possible mediating role of fat-induced T cells. We suspect that these T cells promote diabetes by attacking overly expanded fat tissue, causing inflammation of the fat tissue and release of inflammatory factors that interfere with the body's normal response to insulin. As a first step toward validating this hypothesis, this project will identify these T cells and examine their pathological activities in obese mice. The outcome of this project may provide rationale for therapeutic targeting of the T cells as a novel, and potentially more effective, strategy for preventing and/or curing type 2 diabetes in obese patients.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
For those who suffer from diabetes due to obesity, this project may help them by providing the scientific understanding of the disease process for uncoupling diabetes from obesity. Specifically, we envision that down the road, it may be possible to treat obesity-induced inflammation by suppressing fat-induced T cells, thereby diminishing the impact of obesity on diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
As an immunologist, I am interested in the role of the immune system in health and disease. For years I have been studying type 1 diabetes, a bona fide autoimmune disease. It is natural for me to get involved in type 2 diabetes also, as I have realized that it too is, at least partly, an immune disease. As I am still in the stage of developing a solid hypothesis, this award will enable me to conduct initial experiments and generate preliminary results that are necessary for testing, and refining, my ideas.
In what direction do you see the future of diabetes research going?
As for any disease, the treatment options for diabetes are limited only
by our understanding of the disease process. Diabetes, particularly type
2 diabetes, which accounts for 90% of diabetes cases, has thus far been
viewed and treated as a metabolic disease. Only recently has the role
of the immune system in the disease process been recognized. With this
new understanding, the future of diabetes research will not only
continue to reveal the complexity of the disease, but also offer an
array of new treatment options, including immune-based therapies, for
effective control of the disease.
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