The speed and voracity with which our innate immune system responds to invaders is great – until it turns against us. That happens in autoimmune conditions like lupus, and researchers have been trying to better understand how the system gets so out of control. In a new study, not only have scientists identified a new control mechanism that can trigger lupus, but also traced it back to a single genetic mutation.
The team, based at the Max Planck Institute for Infection Biology, focused on
However, for this response to happen quickly and with appropriate strength, immune cells are constantly producing and degrading receptors to maintain a balanced number of them. Too many, and things can go wrong, increasing the chance of the immune cells reacting against the body’s own cells and leading to lupus.
“From earlier experiments in mice carried out a few years ago at the University of Berkeley in California, we already knew that too many of these receptors are a problem,” explained group leader Olivia Majer in a
To figure out how a cell could end up with too many receptors, Majer and the team looked toward the molecules that help to break them down. In doing so, they identified a protein complex called BORC and demonstrated that this requires another protein, UNC93B1, in order to degrade TLR7.
Neither BORC nor UNC93B1 had previously been associated with
“When I got the first call from Fabian Hauck, I thought it was too good to be true,” says Majer, “but within eight busy weeks of joined effort, we were able to confirm that the mutation in UNC93B1 was the cause of this patient’s lupus.”
Lupus is
It’s hoped that by identifying this new mechanism and the role of UNC93B1, testing for mutations in the protein could become a new part of lupus treatment. With further research, it may even represent a new therapeutic target for minimizing or stopping the damage caused by the disease in the first place.
The study is published in the journal