2009 General Immune System Function
S1P1 receptor in regulatory T cells and lupus pathogenesis and therapy
In a normal immune system, a specialized subpopulation of T cells—“regulatory T cells”—help to control, balance, and dampen activation of the immune system.
Could problems in the regulation of this pathway hold clues as to why the immune system becomes hyperactive and uncontrolled in lupus?
Dr. Chi’s lab has discovered a novel pathway that interrupts the function of these regulatory T cells. With LRI funding, he will investigate the pathway’s molecular mechanisms and assess whether it can serve as a drug target to suppress the agitated immune system response of lupus.
Newly published NIH-funded research stemming from the above work funded by the Lupus Research Institute discovered that the protein PTEN known to stop tumors from forming also helps prevent autoimmune diseases by stopping the immune system from reacting. The recent work provides a new direction for research into better treatments for lupus and other autoimmune diseases.
Dr. Hongbo Chi at St. Jude Children’s Research Hospital explains how the initial study funded by an LRI Novel Research Grant opened the door to his current work:
“We were able to identify the molecular pathways that impact the function of regulatory T cells (Tregs). Tregs are a unique population of white blood cells that helps to maintain immune system balance and keep inflammation in control. Loss of function of Tregs has been implicated in the development of lupus, but the control mechanism has been elusive.” Until now.
"In humans we know that loss of PTEN leads to tumors. This new study highlights another role and shows that PTEN is also crucial for proper functioning of regulatory T cells and prevention of autoimmune diseases," said Dr. Chi. "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."