Maternal Factors Induces Autism-like Phenotypes in Mice

Friday, May 12, 2017: 5:00 PM-6:30 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
J. R. Huh, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA

 Human epidemiological studies point to a critical role for immune dysregulation in maternal womb as a risk factor in Autism Spectrum Disorder (ASD). This observation, coined maternal immune activation (MIA), has been modeled in mice by inducing inflammation in pregnant dams. However, The immune cell populations critical in the MIA model have not been identified


We tested whether inflammatory T helper cells producing interleukin-17 (Th17 cells) are necessary for MIA-associated phenotypes.


We used both genetic mutants and blocking antibodies to investigate the roles of maternal Th17 cell pathway in promoting MIA associated phenotypes.


T cell-specific inactivation of RORγt in mothers (thus selectively removing Th17 cells in pregnant mothers) protected from induction of MIA-dependent behavioral phenotypes in offspring. In addition, we found that MIA leads to abnormal cortical phenotypes in offspring and this malformation is fully rescued by inhibiting the maternal Th17 cell pathway. We also showed that the receptor for IL-17 (IL-17Ra) is expressed in the developing fetal brain and its expression is increased in the cortex upon MIA.


These observations collectively suggest a hypothesis that uncontrolled activation of IL-17Ra expressed in fetal brain induces abnormal cortical development and these structural abnormalities may be an underlying cause of the MIA-dependent autism-like phenotypes.