July 13, 2020

“Nur” target may aid arthritis treatment

Vanderbilt immunologists have discovered that the protein Nur77 is part of a control mechanism that guards against autoimmunity in natural killer T cells.

Semi-invariant natural killer T (iNKT) cells are a type of white blood cell that helps the body defend against infection and maintain homeostasis. This defense mechanism should be optimal, as an unbridled iNKT cell-mediated response can cause inflammatory disease.

Nur77 is a transcription factor that limits inflammation and autoimmune conditions in animal models. Its role in iNKT cells previously was unclear.

Reporting in the Proceedings of the National Academy of Sciences, Sebastian Joyce, PhD, and colleagues found that iNKT cells failed to develop in mice when Nur77 was overexpressed in T-lineage cells of the thymus. Nur77 also controlled the induction in iNKT cells of self-tolerance — the ability to recognize and yet “tolerate” the body’s own antigenic molecules.

These findings suggest Nur77 is part of a control mechanism that ensures iNKT cells do not “go rogue” and cause autoimmune or auto-inflammatorydiseases. Nur77 thus may be a target for clinical intervention to treat diseases including arthritis and COVID-19, the researchers concluded.

The research was supported by National Institutes of Health grants AI137082, AI061721, AI042284, DK081536, DK104817 and AI139046, the American Heart Association and a Veterans Administration Merit Award.