Public Release: 

Prooxidants may fix metabolic defect in arthritis-driving T cells

American Association for the Advancement of Science

IMAGE

IMAGE: Rheumatoid arthritis is a common autoimmune disease involving joint inflammation and damage. Researchers have uncovered a metabolic defect in T cells from rheumatoid arthritis patients, which may be corrected by... view more

Credit: V. Altounian / Science Translational Medicine (2016)

Researchers have uncovered a metabolic defect that spurs T cells to go rogue in rheumatoid arthritis patients. The findings suggest that prooxidants, chemicals that generate reactive oxygen species (ROS), rather than antioxidants that protect against ROS, may help fix this metabolic malfunction and quell joint inflammation. Rheumatoid arthritis is a common autoimmune disease in which overactive T cells trigger joint damage and inflammation. To better understand the metabolic underpinnings of this disease, which have been unclear, Zhen Yang and colleagues analyzed rheumatoid arthritis patients' T cells, which they also transferred into human joint tissue-engrafted mice. The researchers found that an imbalance in glucose metabolism can drive T cells to abnormally proliferate and spur inflammation. Instead of breaking down glucose to form ATP or energy like healthy T cells do, patient-derived T cells shunted glucose into the pentose phosphate pathway, which generated building blocks for new T cells as well as a molecule, called NADPH, that counteracts ROS toxicity. While some ROS are notorious for damaging tissues, they have also recently been understood to play an important role in regulating cell growth and survival. By reducing ROS levels, NADPH fueled reductive stress in T cells that accelerated their proliferation and conversion into pro-inflammatory T cells. What's more, treating arthritic mice with ROS-inducing drugs restored the T cells' redox balance and reduced joint inflammation. A related Focus by George Tsokos discusses how replenishing ROS may offer a potential anti-inflammatory strategy for treating rheumatoid arthritis.

###

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.