It’s about preventing infection without triggering autoimmunity. Researchers at Sylvester Comprehensive Cancer Center and the University of Miami Miller School of Medicine identified a cellular protein and pathway that activates our immune system to fight against bacteria or virus infection. Too little and the infection progresses, too much and a person could develop an autoimmune condition.
The finding builds on earlier research from the same team, work that led to the discovery of the stimulator of interferon genes (STING) protein pathway. Importantly, an overactive STING response can cause chronic inflammation.
“STING is essential for protecting us from harmful infection. However, if STING is activated too much, then harmful levels of cytokines can accumulate in our body and cause inflammation and autoimmune disease,” said Glen N. Barber, Ph.D., Eugenia J. Dodson Chair of Cancer Research at Sylvester and professor and chair of the Department of Cell Biology at the Miller School.
Importantly, these scientific findings come with clinical implications. This pathway could be involved in conditions like inflammatory bowel disease, systemic lupus erythematosus, and a host of other diseases triggered by inflammation. “In cases where patients, especially infants, are possibly exhibiting inflammation-related disease, it is possible to determine if defects in STING signaling or other innate immune pathways are involved,” Barber said. “In the future, drugs that target these pathways may be used to control cytokine production and avert disease.”
“We knew STING was important in host defense against microbial infection, but we were a little surprised that STING was also so important in inflammation,” Barber said. He and his team in the Department of Cell Biology are on the forefront of this research, having been the first to discover STING and STING-dependent signaling. STING signaling has also now been found to be critically important in fighting cancer too, he added.
Along with colleagues Guoxin Ni and Hiroyasu Konno, Ph.D., Barber used mass spectrometry to identify chemical changes in the STING protein pathway through a process called ubiquitination. Under normal conditions, ubiquitination switches STING on to the right amount when it’s time to fight off microbial infection. However, controlling these events may help prevent certain inflammatory diseases, in cases where STING is too active.
Going forward, the investigators hope to identify the ubiquitination ligases responsible for modifying and controlling STING. “We have already found one, reported in this paper as MUL1,” Barber said. “These ligases may be good targets to develop drugs to prevent inflammatory disorders.”
The full study details were published May 5, 2017, in the journal Science Immunology.
Miller School of Medicine