A link between immune signaling and ASD

Maternal immune activation acts through interleukin-17a to promote ASD-like phenotypes in mice

Interleukin-17a (IL-17a) is a protein produced by activated T cells as part of the immune system’s response to infection. It promotes inflammation, and is associated with rheumatoid arthritis and psoriasis. Elevated IL-17a levels have been found in autistic children, and the IL17A gene is among many genes enriched in autistic patients. SCSB Investigators Gloria Choi and Jun Huh studied interleukin-17a (IL-17a) in mice, modeling maternal immune activation (MIA) during fetal development. Pregnant mice were subjected to immune system activation by injection of poly(I:C), which mimics viral infection.

The image illustrates a maternal immune cell population (Th17cells) influencing fetal brain development during pregnancy to result in the cortical malformation. Round-shaped objects represent Th17 cells floating on colored streams, representing other maternally derived factors that support fetal development. The ripple on the surface of the brain indicates the cortical malformation, the pathological phenotype observed in the MIA-affected offspring. Layered structures of the cortex are illustrated with stripes of varying colors.

Image: McGovern Institute for Brain Research

Immune activation in the dams resulted in increased IL-17a mRNA expression in fetuses, abnormal cortical development, and communication and other behavioral changes in offspring. Direct application of IL-17a into fetal brain had similar effects, while all the effects could be rescued by blocking maternal IL-17a production. This study provides direct evidence of a role for MIA in the pathogenesis of ASD-like behavioral and cortical phenotypes in mice.

Learn more at the McGovern Institute or read the original research at Science (subscription content).

Written by T. Emery for SCSB