The UC Davis MIND Institute announced on Apr. 2 two new studies investigating the role of regulatory T cells (Tregs) in neuroinflammation and behavioral changes related to autism.
Tregs, which act as immune system "brakes" to reduce inflammation, are often found at lower levels in individuals with autism. Researchers have previously observed increased inflammatory immune cells in people with autism, a response associated with greater behavioral support needs. Higher Treg levels have been linked to improved behavioral outcomes, but their function in autistic children remains underexplored.
The first study, published in the Journal of Neuroinflammation, focused on characterizing Tregs in children with autism and determining whether gastrointestinal issues influenced these cells differently. The researchers compared the number and genetic activity of Tregs between 36 children with autism and 18 typically developing children who participated in the ongoing CHARGE study. They found that autistic children had both altered numbers of Tregs and differences in gene expression compared to their peers. Genes involved in DNA repair and metabolism were upregulated, while those related to energy production were downregulated. The findings suggest that the identity of Tregs may be unstable among autistic children, particularly those exhibiting more challenging behaviors.
A second study used a mouse model known as maternal immune activation (MIA), which produces offspring displaying behaviors similar to those seen in autism. Researchers transferred healthy mouse Tregs into male and female MIA mice to observe effects on tissues commonly inflamed by autism-related conditions: blood, brain, and gut. Significant sex differences emerged; male mice showed greater improvements after receiving the cell transfer than females.
"Transferring Tregs reduced inflammation and improved brain and behavioral outcomes in the MIA model, with the most significant benefits seen in male mice," said Paul Ashwood, senior author of both studies from UC Davis Department of Medical Microbiology and Immunology.
Ashwood said: "These results suggest that Treg therapy could be a promising approach for reducing inflammation and related impacts in conditions linked to maternal immune activation and neurodevelopmental conditions such as autism." The researchers acknowledged limitations including small sample sizes for human subjects and timing issues regarding when transfers occurred during development for animal models.
