A multidisciplinary research group at the University of Michigan, spanning microbiology, dermatology and rheumatology, discovered that IRE1α orchestrates the release of neutrophil extracellular traps, or NETs, from lupus neutrophils. NETs are sticky, spider web-like structures that cause inflammation when released at the wrong time or in the wrong place.
NETs play an important role in the pathogenesis of lupus and other autoimmune diseases, where they trigger autoantibody formation and contribute to blood vessel clotting and damage.
Thanks to the previous work of study authors Basel Abuaita, Ph.D. and Mary X. O’Riordan, Ph.D., microbiologists and immunologists at Michigan Medicine, the research group knew that the IRE1α pathway was important for neutrophil activation in models of another potentially deadly disease, Staphylococcus aureus infection.
“Given that neutrophils are over-activated in lupus, we hypothesized that the IRE1α pathway might be part of the story in this disease, too,” says Gautam Sule, Ph.D., a postdoctoral fellow in rheumatology at Michigan Medicine. “It’s what prompted this collaboration, and the result was the discovery of an abnormally activated IRE1α pathway in lupus patient neutrophils, which tracks closely with disease severity.”
However, this new study posed unique challenges, because according to study author Jason S. Knight, M.D., Ph.D., a rheumatologist at Michigan Medicine, neutrophils aren’t easy to study.