News Brief by Fred Lu
In 2010, Caltech Professor Paul Patterson presented a study to a room full of graduate students which examined all Danish children born between 1980 and 2005. The study showed a correlation between severe infections requiring hospitalization during pregnancy and autism. Among the graduate students in attendance that day were Gloria Choi and her husband Jun Huh, now Assistant Professors at MIT and the University of Massachusetts Medical School. Patterson was interested in the role that an immune signaling molecule called interleukin 6 (IL6) played in the development of autism like behaviors in rodent models of disease.
Coincidentally, Huh realized that the TH17 immune cells that he was studying were also activated by IL6 and began to investigate the role of Th16 in the development of inflammation. After injecting pregnant mice with double stranded DNA designed to trigger an immune response, they found that the offspring displayed issues with sociability, communication, and developed repetitive behaviors – confirming results from previous studies. However, they also discovered that if they suppressed TH17 activity in infected mothers by either knocking out a transcription factor needed for TH17 differentiation or by blocking interleukin 17 (IL17), a protein produced by TH17, the offspring would display normal behaviors. Fetal mice of mothers experiencing an inflammatory reaction had both high levels of IL17 and cortical mis-patterning similar to developmental abnormalities found in some patients with autism.
Based off of these results, which were published in Science, the team is looking forward to investigating the biological mechanisms linking inflammation to autism like behaviors in mice with an eye towards reducing the risk of autism in human parents.
Choi, G., Yim, Y., Wong, H., Kim, S., Kim, H., & Kim, S. et al. (2016). The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring. Science. http://dx.doi.org/10.1126/science.aad0314
Massachusetts Institute of Technology. (2016, January 28). How severe maternal inflammation can lead to autism-like behavior: Immune molecules in infected mothers tied to brain and behavior abnormalities in offspring.ScienceDaily. Retrieved February 3, 2016 from www.sciencedaily.com/releases/2016/01/160128152147.ht