Multiple Sclerosis Society of Canada

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MS Society funded postdoctoral fellow uncovers genetic make-up of immune cells implicated in MS

Background:

Microglia are cells of the immune system that are found in the central nervous system (CNS, consisting of the brain and spinal cord). Microglia protect the CNS from harmful infectious agents by releasing pro-inflammatory and anti-inflammatory signals, but recently there has been a debate as to whether these cells are “good” or “bad” in MS. There is research showing that microglia promote inflammation, demyelination and neurodegenerationMS, likely by triggering harmful immune T cells. On the other hand, there is evidence suggesting that microglia have neuroprotective roles in MS. To better understand the role of microglia in MS, researchers must first gather fundamental knowledge about microglia and their activity.

Researchers, including MS Society postdoctoral fellowship recipient Dr. David Gosselin from the University of California, San Diego, recently uncovered new information about the the genetic makeup of microglia, and published these findings in the well-renowned journal Science.

The Study:

Brain tissue was obtained from 19 individuals that were undergoing surgery for seizures, brain tumors and stroke-related events. The tissue was collected from areas that were not affected by the disease. Tissue was also taken from mice to examine differences in genes of microglia from humans and mice. The researchers used a variety of techniques to identify genes present in the microglia, and observed changes in properties over time in microglia which were grown in the lab to determine if they behave differently than in their natural environment in the brain. Finally, the research team further advanced this project by examining the genes found in microglia and identifying the ones that are also implicated in neurological disorders.

Results:

The team found that certain genes associated with neurodegenerative disorders are present in higher quantities in microglia compared to other cells in the brain. Furthermore, when microglia are taken out of their environment in the CNS and grown in the lab, quantities of over 2,000 genes were reduced, suggesting that the activity and genetic properties of microglia depend on signals from their environment. When examining the genes found in microglia in humans versus mice, the researchers discovered that many of the genes associated with neurological diseases were not as highly expressed in mice compared to humans. Finally, the researchers discovered 42 of the genes that are linked to MS are also found in microglia.

Comment:

These fundamental results enhance our understanding of the genetic make-up of microglia, as well as provide a window in to many neurological ailments such as MS. Future work is still required to figure out how microglia can be changed so that the beneficial role of microglia can be targeted while preventing the harmful roles.

Source:

Gosselin D et al. (2017) An environment-dependent transcriptional network specifies human microglia identity. Science. 10.1126/science.aal3222. [Epub ahead of print].