Imbalances of the immune system caused by cells that are overactive or immunosuppressive often lead to a wide range of diseases such as psoriasis or cancer. By regulating the function of a certain class of immune cells, T cells, researchers can help the immune system restore balance and further develop new treatments to combat these diseases.
Researchers at the Gladstone Institutes in the United States, together with the research team at Tsinghua University's School of Pharmacy, School of Medicine and Agios Pharmaceuticals, for the first time revealed a method and mechanism for specific T cell reprogramming. More precisely, they discovered how to transform pro-inflammatory cells that stimulate the immune system into anti-inflammatory cells that suppress the immune system, and vice versa. This important research was published online on August 2, 2017 in the internationally renowned journal Nature.
The researchers focused on two types of cells: one called effector T cells, whose main function is to activate the immune system to protect our body against different pathogens; the other is called regulatory T Regulatory T cells, whose main role is to help regulate the immune system and prevent it from attacking healthy cells and organs in the human body.
Dr. Ding Sheng, a senior researcher at the Glasgow Institute, said: "Our research findings will have a major impact on the treatment of autoimmune diseases and stem cell and immune tumor treatment." Dr. Ding Sheng also served as Dean of the School of Pharmacy at Tsinghua University. The director of the Global Health Drug Discovery Institute (GHDDI), co-founded by the Gates Foundation, Tsinghua University and the Beijing Municipal Government.
Using his expertise in drug discovery, Dr. Ding Sheng's research team has identified a small molecule drug that can successfully reprogram a pro-inflammatory effector T cell into an anti-inflammatory regulatory T cell. The findings, published in the journal Nature, detail the metabolic mechanisms of this type of cell transformation.
This new approach to T cell reprogramming has the potential for a variety of medical applications. For example, in autoimmune diseases, over-excited effector T cells can cause damage to the body. The conversion of these cells into regulatory T cells helps to reduce the overactivity of the immune system, restore it to equilibrium, and ultimately treat the disease.
In addition, the study can also be used to improve stem cell therapy. At least in theory, the production of regulatory T cells can promote immune tolerance and prevent the body from rejecting newly transplanted cells.
“Our research is also helping to further develop immuno-oncology and cancer treatment,†explains Xu Tao, the lead author of the paper and postdoctoral researcher at Dr. Ding Sheng’s laboratory. “This type of treatment is not directed at cancer. It is by activating the immune system to recognize and attack cancer cells."
Many types of cancer suppress immune system function through regulatory T cells, making tumors difficult to detect by the immune system, thus creating an enabling environment for the continued growth of tumors. In this case, Dr. Ding Sheng's team's research can transform regulatory T cells into effector T cells to strengthen the immune system's function, allowing it to better identify and destroy cancer cells.
The study was supported by the Glaston Institute and Tsinghua University.
Remarks: Other authors of the paper include Katerina Akassoglou, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Saiyong Zhu, Nan Cao and Yu Zhang from the Glaston Institute; and from Agios Pharmaceuticals Edward M. Driggers, Kelly M. Stewart and Dongwei Zhu; Chen Dong, Xiaohu Wang and Lu Ni from Tsinghua University School of Medicine, China.
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