Tumor suppressor protein plays key role in maintaining immune balance

St. Jude Children’s Research Hospital scientists have discovered that a protein widely known for suppressing tumor formation also helps prevent autoimmune diseases by putting the brakes on the immune response. The research was published recently online ahead of print in the scientific journal Nature Immunology.

Researchers showed that the tumor suppressor protein PTEN is essential for the proper functioning of regulatory T cells. This small population of white blood cells helps to maintain immune system balance by suppressing specialized T cells called helper T cells that fuel distinct parts of the immune response. The helper T cells investigated in the study included type 1 T helper (Th1) and follicular T helper (Tfh) cells.

The interplay between regulatory T cells and helper T cells is crucial both for combating infections and for preventing misguided immune attacks that lead to autoimmune diseases and other problems. Details of how regulatory T cells control the diverse functions of various helper T cells have been elusive, however. The study fills key gaps in that understanding, particularly PTEN’s role.

PTEN is known as one of the most frequently altered tumor suppressor genes in human cancers, but loss of the protein has also been tied to autoimmune problems. The study showed that is because PTEN is required to maintain the stable population of regulatory T cells that keeps the immune system in check.

Working in specially bred mice, researchers showed that deleting the PTEN gene in regulatory T cells was followed by a dramatic increase in the number of Tfh and related cells. Tfh cells aid production of antibodies, which combat infections. But when produced inappropriately, antibodies can also drive autoimmune disorders such as lupus. The study mice developed kidney damage and immune changes associated with lupus. Restoring PTEN to 50 percent of normal levels did not protect the mice from inflammatory disease.

Researchers found evidence that Th1 cells influence the activity of Tfh cells. Th1 cells produce the chemical messenger interferon gamma that revs up the immune response. When researchers blocked interferon gamma production in the specially bred mice, the number of Tfh cells fell along with lupus-like immune abnormalities.