Tumor Suppressor Protein Is Crucial In Maintaining Immune Balance And Unveil Lupus

Researchers from St. Jude Children’s Research Hospital found that a protein involved in tumor formation suppression also plays a role in preventing autoimmune diseases and other problems through decelerating the immune response. The study was published in the Nature Immunology journal.

The research team found that the tumor suppressor protein (PTEN) is essential for correct functioning of the regulatory T cells. This group of white blood cells helps to maintain the immune system balance through suppressing specialized T cells called “helper T cells” that serve as fuel to different sets of the immune response. In this study, follicular T helper (Tfh) cells and type 1 T helper (Th1) were assessed.

The reciprocity between helper T cells and regulatory T cells is a key point for attacking infections and to prevent misplaced immune attacks that can ultimately lead to autoimmune diseases and other issues. This study is important in order to understand the role of PTEN and to identify a new way to improve treatment for autoimmune conditions.

PTEN, known as a tumor suppressor gene in human cancers, is also tied to autoimmune problems. Through this study, researchers found that PTEN is important to keep the group of regulatory T cells stable.

Hongbo Chi, author of the study, said in a press release: “In humans we know that loss of PTEN [gene] leads to tumors. This study highlights another role and shows that PTEN is also crucial for proper functioning of regulatory T cells and prevention of autoimmune diseases. In mice, the loss of just one copy of the PTEN gene in regulatory T cells is sufficient to set the stage for autoimmune problems.”

When the PTEN gene is deleted, the amount of Tfh and related cells increases and these cells, when produced in a dysfunctional way, can lead to immune disorders like lupus. Th1 cells can interfere with the activity of Tfh cells and, in turn, Th1 cells produce interferon gamma. When this interferon is blocked, the amount of Tfh cells decreases like some other immune abnormalities like lupus.

“We have identified a crucial role of PTEN in controlling Tfh cells and autoantibody production. Additionally, by linking the role of PTEN to Tfh cells, we have opened doors for further investigation of Tfh related lymphomas. These results reveal a hierarchy of control that regulatory T cells use to simultaneously regulate Th1 and Tfh cells. We showed that Th1 production of interferon gamma is a pre-requisite for the activity of Tfh cells,” added Kai Yang, co-first author.

The study also revealed information about the mTOR pathway that can lead to new treatments in the future: “Our research establishes that the interaction of PTEN and mTORC2 functions as a central pathway to maintain the stability of the regulatory T cell population and to ensure their ability to control the activity of Th1 and Tfh cells.”