2007 Cell Signaling
Enlisting “Big Eater” Cells May Prevent Autoimmune Response
A Lupus Research Institute (LRI) scientist and his team have discovered a new pathway that helps prevent the immune system from mistaking dying cells as a potential threat. Harnessing this protective process could allow researchers to develop new treatments to prevent destructive immune responses in lupus and other autoimmune diseases such as rheumatoid arthritis.
Cell death is a healthy and everyday part of our body’s renewal and repair. But in lupus, dying cells trigger the immune system to mount a devastating attack on cell components, such as DNA. So how are such dangerous responses to dying cells normally avoided?
Dr. Tracy McGaha of Georgia Health Sciences University, Augusta, explains:
“Dying cells are filtered out of the blood as it passes through the spleen, where they are engulfed by scavenger cells known as macrophages, which literally means ‘big eaters.’ Our 2007 grant from the LRI allowed us to pursue our idea that the cells responsible for clearing dying cells from the blood are also responsible for suppressing unwanted immune responses.
Last year we reported in the journal Blood our findings showing that macrophages in the spleen could suppress immune responses to dying cells. We also showed that removing the macrophages caused more severe disease in lupus-prone mice.
Now we are excited to have uncovered how the macrophages stop immune responses to dying cells. As we report in a recent issue of the Proceedings of the National Academy Sciences, we found that macrophages that eat dying cells produce an enzyme, known as indoleamine 2,3-dioxygenase, or IDO, which suppresses neighboring immune cells that could trigger a response to components of the dying cells. Interestingly, the same enzyme IDO is also produced in the placenta, where it helps prevent the mother’s immune system from attacking and rejecting the unborn child.
We are now investigating whether this natural pathway of immune suppression can be ‘re-set’ in lupus patients to stem their autoimmune disease. The possibility of manipulating how IDO functions opens up enormous potential for a new therapeutic target in drug development for lupus and possibly other autoimmune diseases. We are grateful to the LRI for giving us the opportunity to explore what was an entirely novel approach, and we are very excited to see that what was a calculated ‘hunch’ is providing answers.”
LRI President and CEO Margaret Dowd comments, “The LRI is gratified that we too acted on such an innovative hypothesis and awarded a grant to support Dr. McGaha’s proposal. His team’s findings have the potential to make a significant difference for the 1.5 million Americans with lupus as well as the more than 23 million living with other autoimmune diseases.”