A genetic variant associated with an increased risk of multiple sclerosis (MS) due to its impact on certain immune system cells can also affect brain cells called astrocytes, a study shows.
Reported in the study, “Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis,” in the journal Nature Communications, these findings suggest that the malfunctioning of these brain cells may also contribute to MS susceptibility.
More than 200 genetic variants have been identified as risk factors for developing MS, with several of them linked to changes in lymphocytes — cells that mediate the immune system’s overreactive response that characterizes MS.
However, whether genetic variants can also affect brain cells, affecting the function of the central nervous system (brain and spinal cord), remains unclear.
Researchers at Yale University looked at how a particular MS risk variant called rs7665090G, which increases the expression of a key autoimmunity mediator called NF-κB in lymphocytes, may change the function of astrocytes. Astrocytes are a group of star-shaped cells that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation.
“NF-κB plays a critical role in autoimmunity, including in MS, where 18% of all allelic MS risk variants are estimated to affect or intersect with the NF-κB signalling pathway,” the researchers wrote.
NF-κB was previously shown to be capable of activating astrocytes which, once activated, become a source of chemoattractants, substances that can attract cells of the immune system.
Moreover, two previous studies showed that inhibiting NF-κB-mediated activation of astrocytes decreased the infiltration of immune cells into the central nervous system and the damage in the experimental autoimmune encephalomyelitis (EAE) mouse model, an established model to study MS.
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