The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
Department of Medicine, Division of Infectious Diseases and Immunology; Program in Innate Immunity; UMass Metabolic Network
Cell Biology | Cellular and Molecular Physiology | Immunology and Infectious Disease | Molecular Biology
Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor gamma t (RORgammat)-dependent effector T lymphocytes [for example, T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.
DOI of Published Version
Science. 2016 Feb 26;351(6276):933-9. Epub 2016 Jan 28. Link to article on publisher's site
Science (New York, N.Y.)
Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. (2016). The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. UMass Metabolic Network Publications. https://doi.org/10.1126/science.aad0314. Retrieved from https://escholarship.umassmed.edu/metnet_pubs/53