Researchers at Cedars‑Sinai have discovered a “molecular switch” on the PTPN22 gene that triggers T‑cells to become overactive, driving the tissue damage characteristic of lupus.
The preclinical research, reported in Science Advances, examined how phosphorylation of PTPN22 alters T‑cell activation in lupus patients. Using both human tissue and a mouse model of the disease, the team showed that the phosphorylated protein behaves like an on switch, sending immune cells into a hyperreactive state that produces autoimmune pathology, including systemic lupus erythematosus.
National Institutes of Health data indicate that roughly 26 million Americans are affected by an autoimmune disorder. Officials believe these findings could pave the way for novel therapies for this large patient group.
“PTPN22 is one of the strongest genetic risk factors for lupus,” explained Nunzio Bottini, MD, Ph.D., director of the Kao Autoimmunity Institute at Cedars‑Sinai and senior author of the study. “The phosphorylation signal appeared more frequently in lupus patients than in controls.” He added, “When we inhibited this molecular switch in mice, the animals were protected from lupus‑associated complications such as kidney disease.”
Shen Yang, Ph.D., lead author and research coordinator of the Technology Unit at the Kao Autoimmunity Institute, said further research is required.
“Our results suggest that targeting PTPN22 could reset the immune response, preventing the destructive hyperactivity that underlies lupus and other autoimmune diseases,” Yang said.