Lupus Investigator Reveals Enzyme’s Role in Immune Response

A key player the immune system, interleukin-2 (IL-2) regulates white blood cells, helping the body discriminate between its own cells and those of disease-causing invaders. This role makes it relevant to both autoimmune disorders – in which the body attacks its own cells as it would an infectious bacterium – and cancer, which sends signals to evade the immune response. 

George C. Tsokos, MD, Chief of Rheumatology at Beth Israel Deaconess Medical Center (BIDMC), is a leading expert in lupus, a chronic autoimmune disease that causes widespread inflammation and tissue damage to organ systems throughout the body and affects at least 5 million people worldwide. His laboratory studies immune cell signaling and gene transcription in lupus as well as mechanisms of tissue injury. By exploring the molecular origins of lupus, Tsokos and colleagues seek to identify novel biomarkers for diagnosis and targets for the treatment of the disease. 

In new research published in JCI Insight, Tsokos and colleagues investigated the role of an enzyme called phosphatase (PP2A) in IL-2 signaling for the development of a subpopulation of immune cells called regulatory T cells or Tregs. Using mice engineered not to express PP2A in their Treg cells – which causes the animals ultimately to develop autoimmune-related manifestations – the team found that PP2A controls the expression and the function of the Treg receptor for IL-2.

“Regulatory T cells cannot produce IL-2, but they need this cytokine for their development and function,” said Tsokos. “Our previous studies had shown that phosphatase limits the production of IL-2, while requisite for the proper function of Tregs. Because of the dependence of Treg cells on IL-2, it was important to determine whether PP2A affects IL-2 signaling.  Answers to this question will provide us with the tools to manipulate Treg function in autoimmunity and cancer.”