Two new studies from the UC Davis MIND Institute examined regulatory T cells (Tregs) and their potential role in neuroinflammation and behavioral changes associated with autism .
Tregs act as immune system "brakes," calming inflammation to prevent overreaction. They are often decreased in autistic individuals.
Previous studies have found higher levels of inflammatory immune cells in the blood, brain and gastrointestinal tissues of people with autism. These increased inflammatory responses are often linked to greater behavioral support needs, while higher levels of Tregs are associated with improved behavioral outcomes . Despite this, Tregs have not been well studied in autistic children, and their potential as a therapeutic target remains largely unexplored.
The first study, published in the Journal of Neuroinflammation, characterized Tregs in children with autism. It determined if gastrointestinal (GI) issues, a common co-occurring condition , altered Tregs in a unique way.
The researchers found autistic children had altered Tregs both in number and in the genes those cells use. This was compared to typically developing children. All participants were enrolled in the CHARGE study (Childhood Autism Risk from Genetics and Environment), an ongoing study that supports autism research.
The researchers compared the number and type of Tregs in 36 children with autism and 18 typically developing children. They also examined gene expression in Tregs to determine if there were differences between the two groups. In addition, they looked at the relationship between Tregs and gastrointestinal symptoms in autistic children.
The researchers found children with autism showed altered Tregs. Compared to typically developing children, children with autism had:
The upregulated genes mainly help cells reorganize and repair DNA and adjust how they manage energy and fat metabolism. The downregulated genes were mostly involved in energy production, such as the conversion of oxygen and nutrients into usable energy.
The researchers note that more research is needed, but that these changes in metabolism and DNA organization suggest the identity of Tregs is unstable. One commonality was that having fewer Tregs was associated with more challenging behaviors in both typically developing children and children with autism.
“These differences in Treg populations may help explain the higher levels of inflammation seen in autism and could be linked to both gastrointestinal problems and certain behavioral traits,” said Rachel Moreno, a postdoctoral fellow at the MIND Institute and first author of the study. “This data further supports the idea that the immune system plays an important role in autism in at least some individuals.”
There is growing interest in biological therapies for autism that target Tregs.
In a second study , also published in the Journal of Neuroinflammation, the authors assessed whether increasing Tregs could reduce inflammation and behavioral challenges.
They used a mouse model of altered neurodevelopment, maternal immune activation ( MIA ), in which offspring exhibit autism-like behaviors.
The team transferred Tregs from healthy mice into male and female MIA mice, and evaluated tissues commonly inflamed in autism, including blood, brain and gut.
They found significant sex differences in the MIA mouse offspring that received the Treg transfer, with males showing greater changes than females.
Male mice showed:
Female mice showed:
“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. Ashwood is a professor in the UC Davis Department of Medical Microbiology and Immunology and a faculty member with the UC Davis MIND Institute.
“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,” Ashwood said.
The researchers noted several limitations. The first study was limited by its small sample size. In the second study, the Treg transfer occurred at 10 weeks, and transferring into younger mice (when the immune and brain systems are still developing) may be more relevant for inflammation than for behavior modification.
Full lists of co-authors can be found in the papers.
Journal of Neuroinflammation
Experimental study
People
Altered phenotype and gene expression of regulatory T cells (Tregs) in children with Autism, and the relationship with comorbid gastrointestinal symptoms
17-Feb-2026
The authors declare no competing interests.