Augusta, Ga. Cells that die naturally generate a lot of internal debris that can trigger the immune system to attack the body, leading to diseases such as lupus.
Now Georgia Health Sciences University researchers report that an enzyme known to help keep a woman's immune system from attacking a fetus also helps block development of these autoimmune diseases that target healthy tissues, such as DNA or joints.
The findings point toward new treatment strategies for autoimmune diseases, which are on the rise in light of a germ-conscious society that regularly destroys many of the previously pervasive microbes that made the immune system more tolerant.
"The basic premise of lupus is you have lost normal tolerance to yourself, your own proteins and DNA," said Dr. Tracy L. McGaha, GHSU immunologist and corresponding author of the study published in Proceedings of the National Academy of Sciences.
They found that IDO, or indoleomine 2,3-dioxegenase, helps promote tolerance to debris generated by natural cell death and that when IDO is removed from the mix, the debris spurs an immune response that can trigger autoimmune disease. In mice genetically programmed to develop lupus, blocking IDO resulted in earlier, more aggressive disease.
"This connects IDO and macrophages. It's a newly described role for IDO in regulation of tolerance toward self," McGaha said. Consequently, increasing IDO production or its downstream effects might be a way to regain lost tolerance, he said.
They studied activity in the spleen, a hard-working immune organ, that constantly filters blood. In a perfectly orchestrated defense, the entrance to the spleen is surrounded by immune cells that scour blood for viruses, bacteria, even fat and cholesterol floating by.
A nearby subset of macrophages, which are essentially scavengers, then capture and consume the undesirables, McGaha said. Interestingly, a lot of what m
|Contact: Toni Baker|
Georgia Health Sciences University