German scientists have discovered the protein that regulates autoimmune diseases. And they have a very special kind of mouse to thank for the discovery that could affect how such diseases are treated.
Rheumatoid arthritis is an autoimmune disease that mostly affects joints like the ones in the hands and feet. A patient’s immune system destroys the connective tissue. Joint capsules become inflamed as a result, leading to swelling and reduced movement in the affected parts of the body. Some 800,000 people suffer from the disease in Germany alone – almost one percent of the population.
Now a team of scientists at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg has made a discovery that helps to better understand autoimmune diseases like rheumatoid arthritis.
The team, which was led by German molecular immunologist Michael Reth, found out that cells are more likely to respond to and spread stimulatory signals, which can lead to illnesses like arthritis, when their B-lymphocytes lack a protein called PTP1B. Fewer or less-active PTP1B proteins make for a more severe autoimmune reaction in which the body attacks perfectly healthy tissue.
“The surprising finding was that B-cells are involved in the disease this way,” Michael Reth told DW. “B-cells are normally put in one drawer – once activated, they produce antibodies. But we now found that B-cells also have another role. They can be involved in general immunity in more regulatory terms as well.”
PTP1B is a gatekeeper. It needs to be present in full force in order to stop the toxic signals from spreading and thus prevent the body from attacking its own tissue like it does in someone with rheumatoid arthritis.
Finding out how the protein works was an important discovery, but it doesn’t come with a solution to help heal arthritis, Michael Reth said. For that, scientists would need to artificially stimulate the PTP1B protein, and they are yet to find a simple way to do that.
“In the pharmaceutical industry, there are many developments to generate inhibitors,” the molecular immunologist explained. But stimulating or even creating a protein in a patient is a different ballgame.
“There isn’t really a drug that can do this,” Reth said. “Inhibiting something is the daily life of many drug developers, of course, but to increase an activity is very difficult.”
The lucky mouse
There are far too many proteins to look at each one individually and test whether it can stop signals and prevent inflammation. Reth and his colleagues found the PTP1B protein at the center of their study by chance.
The scientists were able to discover the useful properties of PTP1B because they were working with the right kind of mouse that another research group had created. The mice were genetically engineered in a way that allowed the researchers to “delete” the PTP1B protein from their B-cells and investigate the effects.
“We then just said, ‘Let’s give it a try and see what this one is doing,'” Reth said. “So it was just availability of material and genetic models that started this project.”