Astrocytes can change hats
Astrocytes, once viewed as passive support cells in the brain, can become cells that regulate the immune system, Emory researchers have demonstrated. The results were published in Neuron on March 30.
When exposed to sustained inflammatory signals, astrocytes can become antigen-presenting cells, which direct the responses of immune cells. But if those signals are removed, the astrocytes return to a quiescent state.
The observation has implications for efforts to control and reverse inflammation in the nervous system, which drives autoimmune disorders such as multiple sclerosis and contributes to neurodegenerative diseases such as Parkinson’s.
“If we know the factors that induce the inflammation and can quench them, then the astrocytes go back to normal. It could have been a one-way journey,” says Emily Hill, PhD, a former graduate student in Steven Sloan’s lab and lead author of the paper.
In the immune system, antigen-presenting cells play a role analogous to security cameras; they present information about what they “see” and are part of a decision about whether to trigger a general alarm.
Neuroscientists have been revising their view of astrocytes, which outnumber neurons in many regions of the brain. Astrocytes have been reported to act as antigen-presenting cells before, but Hill and her colleagues were able to detect molecules that are markers of “professional” antigen-presenting cells, which are more specialized. These markers are called MHC class II, and allow interaction with helper T cells, a critical element of the immune system.
The team studied astrocytes in brain organoid cultures, which simulate aspects of human fetal brain development, and confirmed the findings in samples of adult human brain tissue.
The authors found that after inflammatory prodding, astrocytes still don’t carry all of the molecules needed for full stimulation of T cells. This raises the possibility that astrocytes may actually help control neuro-inflammation by promoting immune dampening rather than activation, Sloan says.
“Understanding how inflammation affects the brain is essential to address both autoimmune and neurodegenerative disorders,” he says.
Sloan’s team completed this work at Emory's Department of Human Genetics; his lab is now based at the Netherlands Institute for Neuroscience.