The immune system is responsible for more than keeping us safe against infectious diseases. According to a new study by associate professor A. Kimberley McAllister at UC Davis, immune system molecules also regulate neural connections as the brain develops. This research could provide clues to environmental causes of disorders like autism.
The molecule is a protein called Major Histocompatibility Complex type 1 (MHC 1). Its role in the immune system is to distinguish between “Self” cells that belong in the body from “Non-self” cells that could be infectious or cancerous. MHC 1 creates peptide tags, derived from cell proteins, which mark cells as healthy; if a cell is infected, proteins from the infectious agent such as a virus will be included in these peptides. Other immune molecules then survey the peptides and kill the infected cell.
Previous research had already found that MHC 1 is present in the brain during early postnatal development.
“Up until about 10 years ago, we didn’t know immune cells were in healthy brains at all,” McAllister said.
McAllister and her team of graduate students and postdoctoral researchers wanted to find out what role MHC 1 played in the developing brain. They studied mice and rats that had differing levels of MHC 1 on the surface of the brain, from none at all to a very high density of the protein on each brain cell. They found that when there were more immune molecules on a brain cell, that cell established fewer connections, called synapses, with neighboring brain cells. The final data showed that fewer immune molecules corresponded to a greater number of connections.
“The molecules [MHC 1] play an important role in regulating connectivity in the brain,” said McAllister. “MHC 1 may be a readout of synaptic activity.”
The researchers aren’t yet sure how MHC 1 attaches to brain cells, but they hypothesize that a molecular signal in the brain determines how many connections to make. MHC 1 may be essential to this process.
The results of this research are surprising, because large molecules like MHC 1 cannot usually travel into the brain. The brain is protected by a layer called the blood-brain barrier (BBB), which acts like a filter. Despite this barrier, densities of MHC 1 can still change depending on the brain’s need.
Scientists do have a hunch for how levels of MHC 1 manage to change: much smaller proteins called cytokines, which can cross the BBB, regulate MHC 1.
“The idea is that cytokines get altered during a systemic immune response, cross the BBB and then alter expression of MHC 1 on neurons which, based on our results, could then alter connections in the developing brain,” said McAllister. “That implication is the most exciting because it implies a mechanism by which environmental insults might be linked to changes in brain development.”
Autism, schizophrenia and other disorders are associated with connectivity changes in the brain. Although McAllister’s study didn’t research whether there is a direct link between MHC 1 densities on brain cells and disorders such as autism or schizophrenia, the research did show a possible molecular pathway through which immune response could affect brain development.
“MHC 1 is important for establishing the right number and type of connections,” said McAllister. “When the number and type of connections are incorrect, it can lead to developmental disorders.”
The field of neuroimmunology is still relatively new to neuroscience. Some disorders, such as the autoimmune disease multiple sclerosis, have a clear link between immune function and neurological symptoms. Other disorders, such as autism or schizophrenia, have causes that are less clear.
“The field of neuroimmunology is really new and we don’t know much about it, which makes it a fascinating topic to study,” said McAllister.
AMY STEWART can be reached at science@theaggie.org.
