Understanding How Microglia Develop in the Brain

Three strands of DNA run horizontal, and each strand has sections of DNA wrapped around histones and other sections that are open.

Stock image of DNA (orange) and histones (dark blue).

Microglia are a type of immune cell found in the brain, and these cells are responsible for development and maintenance of a healthy brain throughout life. Dysregulation of microglia is also observed in neurodegenerative diseases, such as Alzheimer’s disease.

Interferon regulatory factor 8 (IRF8) is a transcription factor that is highly expressed in microglia, suggesting that it helps program the identity and activities of microglia. However, the contributions of IRF8 to microglial development and function are unclear.
In a study from the Ozato Lab, researchers used a mouse model to explore the role of IRF8 in microglial development. They found that IRF8 acts on the development of microglia after birth and steers processes including transcription, chromatin accessibility, and DNA methylation that collectively contribute to microglial identity.
Furthermore, in a mouse model of Alzheimer’s disease, the team found that deleting IRF8 reduced the interaction of microglia with beta amyloid plaques, reduced the size of plaques in the brain, and alleviated the loss or death of neurons.
The findings demonstrate the essential role of IRF8 in setting the genetic landscaped needed for microglia development after birth, as well as its role in the progression of Alzheimer’s disease.

Reference

Saeki K, Pan R, Lee E, Kurotaki D, and Ozato K. IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs. Nature Immunology DOI: 10.1038/s41590-024-01962-2 (2024)

Learn more about the Genetics and Epigenetics of Development Group: https://www.nichd.nih.gov/about/org/dir/affinity-groups/GED.