Shutting off Immune System Signal May Lead to Better Arthritis Treatments

July 6, 2009

New research from the Imperial College London may lead to the ability to turn off an immune system signaling molecule that can contribute to the chronic joint inflammation of rheumatoid arthritis.

New research from the Imperial College London may lead to the ability to turn off an immune system signaling molecule that can contribute to the chronic joint inflammation of rheumatoid arthritis (RA).

Dr Kim Midwood, of the Kennedy Institute of Rheumatology at Imperial College and lead author of the study, and fellow researchers discovered that the molecular switch tenascin-C can trigger the signal molecule TLR4, leading to activation of the immune system and, in some instances, attacking of the joint, which leads to the “persistent inflammation” of RA. Previous research shows that mice without TLR4 do not show chronic joint inflammation, according to the researchers, which, in combination with the discovery of TLR4’s signal switch, may lead to new therapies that focus on the interaction between tenascin-C and TLR4.

The researchers conducted five studies before reaching this conclusion. According to the team, the studies followed this course:

“One study suggested that tenascin-C was needed to sustain inflammation. The researchers induced joint inflammation in mice with and without the gene for tenascin-C. They found the mice that could produce tenascin-C had severe joint swelling with bone and cartilage destruction, but the mice that could not produce tenascin-C had no swelling or tissue destruction at all.

In a subsequent study, the researchers injected the active part of the tenascin-C molecule into mice joints. They found it caused the joints of the mice to become inflamed and that this reaction was more intense with higher doses.

Another experiment demonstrated that tenascin-C causes swelling in the joints by increasing levels of molecules that cause inflammation. The researchers took human immune cells called macrophages and cells called fibroblasts from the swollen joint of patients with rheumatoid arthritis and added tenascin-C. After the tenascin-C was added, the cells produced more molecules that cause inflammation.”

According to Midwood, the researchers “have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis,” and they are hopeful that it will lead to new therapies that will “reduce the painful inflammation that is a hallmark of this condition.”