title: The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.
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.
authors.affiliation: The McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Gloria B
authors.initials: GB
authors.lastname: Choi
authors.affiliation: The McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Yeong S
authors.initials: YS
authors.lastname: Yim
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA. Institute for Behavioral Genetics, Department of Integrated Physiology, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Wong
authors.affiliation: Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sangdoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kim
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Sangwon V
authors.initials: SV
authors.lastname: Kim
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003, USA. Institute for Behavioral Genetics, Department of Integrated Physiology, University of Colorado, Boulder, CO 80303, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hoeffer
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. Howard Hughes Medical Institute, New York, NY 10016, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.affiliation: Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA. charles.hoeffer@colorado.edu dan.littman@med.nyu.edu jun.huh@umassmed.edu.
authors.forename: Jun R
authors.initials: JR
authors.lastname: Huh
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000627:therapeutic use; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D001522:Behavior, Animal; D001526:Behavioral Symptoms / Q000276:immunology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000187:drug effects / Q000276:immunology*; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D009154:Mutation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*; D000097768:Retinoic Acid Receptor gamma
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma; C098680:Il17a protein, mouse
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