Inflammation During Pregnancy Linked to Autism Through Immune Response

Inflammation During Pregnancy Linked to Autism Through Immune Response

Pregnant women who develop severe infections are known to more frequently give birth to children with autism, and a collaborative team of researchers working with a mouse model have identified a possible reason — the immune cell populations and molecules involved in maternal immune activation can affect fetal brain development. The research suggests that targeting Th17 cells, which contribute to autoimmune disorders such as rheumatoid arthritis, might be a therapeutic avenue for these women and their children.

The paper by researchers at MIT, the University of Massachusetts Medical School, the University of Colorado, and New York University Langone Medical Center, “The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring,” was published in Science.

Viral infection during pregnancy has been previously correlated with the development of autism spectrum disorder (ASD) in infants. A 2010 study in Denmark showed that severe influenza infections, severe viral gastroenteritis and urinary tract infections were associated with autism risk. However, the molecular and cellular players have remained unclear.

In this study, researchers observed that mice offsprings of mothers subjected to infection exhibited deficits in sociability, repetitive behaviors, and abnormal communication, all signs of ASD. When Th17 cells were disabled before the onset of inflammation, the offspring mice did not show such behavioral tendencies. Researchers also treated the mothers with an antibody that blocks IL-17, which is produced by Th17 cells, and found no behavioral abnormalities in the offspring. In the presence of inflammation, the effect of IL-17 was exacerbated in the brain cells of developing fetuses. Moreover, all affected offspring showed defects in cortex region, which controls most cognition and sensory processing. This brain region was not affected when Th17 cells were again blocked in the mother.

Researchers are now investigating possible connections between the cortical changes observed and the behavioral abnormalities. Dr. Gloria Choi, the lead author, said in a press release, “In the mice, we could treat the mother with antibodies that block IL-17 after inflammation had set in, and that could ameliorate some of the behavioural symptoms that were observed in the offspring. However, we don’t know yet how much of that could be translated into humans.”

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