Rheumatoid arthritis is the most common autoimmune disease, affecting around 1 in 100 people. It causes painful and persistent swelling in the joints that can result in damage to the bone and cartilage.
Around half of all patients do not respond to one or more of the treatments currently available, and even these can become less successful over time. The researchers behind the new study say stopping the disease closer to the root of the problem could be the best way to treat it, and their results suggest a new target for therapies.
When a microbe infects the body, the body responds by turning on a molecular switch to set the immune system into action and protect the body from disease. Today's findings show that a signal molecule called tenascin-C can trigger the same molecular switch and also activate the immune system. High levels of tenascin-C present in joints therefore may cause the activated immune system to attack the joint leading to the persistent inflammation of rheumatoid arthritis.
The molecular switch is called TLR4, and is found on the surface of immune cells. Previous research has shown that mice without TLR4 do not show chronic joint inflammation. The researchers hope scientists can develop new treatments that target the interaction between tenascin-C and TLR4, which may help to combat rheumatoid arthritis.
Dr Kim Midwood, lead author of the study from the Kennedy Institute of Rheumatology at Imperial College London, said: "Rheumatoid arthritis is a debilitating and painful disease and, unfortunately, there is no cure. Furthermore, current treatments are not effective for many patients."
"We have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis. We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition," added Dr Midwood.
The researchers reached their conclusions by carrying out five studies. 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.
The authors plan to work out the precise mechanism by which tenascin-C increases these levels of inflammatory molecules in the human joint and try to find ways to inhibit this action.
This work was funded by the Arthritis Research Campaign, The Kennedy Institute of Rheumatology Trustees and an MRC New Investigators Research Grant awarded to K. M. The researchers are also grateful for support from the NIHR Biomedical Research Centre funding scheme.
Lucy Goodchild | EurekAlert!
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy