The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
Year: 2016
Type: article
Abstract: 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 (RORγt)-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.
Source: Science
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, Brain and Behavior Research Foundation, Simons Foundation, Alzheimer's Association, Crohn's and Colitis Foundation of America, Richard and Susan Smith Family Foundation, Crohn's and Colitis Foundation, Searle Scholars Program, Simons Foundation Autism Research Initiative, National Research Foundation of Korea, National Institutes of Health, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: Non-canonical translation in hippocampal mGluR-dependent long-term depression - R, Delineating the Anatomical and Functional Circuitry Underlying Social Learning, G554574313, G5553662238, G5838059030, Akt regulation of synaptic plasticity and behavior, Chemical and genetic studies of RORgamma and its critical roles in IBD, G8125292452, G8403220295, Training Program in Immunology and Inflammation, G95757615
OpenAlex ID: W2253802357