A domestic research team has found that non-neuronal cells in the brain have a switch that turns immune responses on and off, and identified the key gene that controls this switch. The findings are expected to provide crucial clues for uncovering the causes of various brain immune responses, including degenerative brain diseases, and for establishing treatment strategies.
A joint research team led by Jeong In-kyung, a professor in the Department of Biological Sciences at Korea Advanced Institute of Science and Technology (KAIST), and Jeong Won-seok, deputy director of the Vascular Research Center at the Institute for Basic Science (IBS) and a professor in KAIST's Department of Biological Sciences, said on the 24th that it has "for the first time in the world identified that a specific gene in brain astrocytes plays a key role in regulating adult brain immune responses." The study was published online on the 22nd (local time) in the international journal Nature Communications.
Differences in genes that people carry do not cause major problems during early brain development, but it has long been a mystery why some individuals are more susceptible when brain diseases such as dementia occur with age.
Using a mouse model, the researchers conducted a detailed analysis of the gene regulation programs of astrocytes—which account for a high proportion of the brain and spinal cord—across developmental stages. The brain contains neurons that transmit signals and glial cells that support them. Among glial cells, star-shaped astrocytes, or astroglia, supply nutrients to neural tissue.
Gene analysis revealed that the NR3C1 gene is a key regulator in suppressing long-term immune responses during the postnatal developmental stage. The team identified 55 important proteins that regulate genes during astrocyte maturation. Among them, the protein produced by the NR3C1 gene served as the most crucial switch when an infant's brain first develops.
The absence of the NR3C1 gene did not severely impair brain development in childhood. The problem arose in adulthood, with autoimmune disease in which the brain's immune system mistakes neurons for external invaders and attacks them. In this case, without the NR3C1 gene, the brain mounted an excessive inflammatory response and the disease became much more severe.
Jeong In-kyung said, "This study shows that a specific period of astrocyte development can determine vulnerability to brain diseases in adulthood and old age," adding, "It will lead to a new understanding of the pathogenesis of immune-related brain diseases and the development of treatment strategies."
References
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-64088-5