The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring
By G. Choi, Y. S. Yim, H. Wong, Sangdoo Kim, Hyunju Kim, Sangwon V. Kim, C. Hoeffer, Dan R. Littman, Jun R. Huh. Science, 2016
1,096 citations recorded by the source corpus.
A T cell cause for autism? The causes of autism spectrum disorder (ASD) are complex and not entirely clear. Alterations in the mother's immune system during pregnancy, especially during key early periods of fetal neurodevelopment, may play a role. Choi et al. provided infectious or inflammatory stimuli to pregnant mice, which resulted in of spring exhibiting behaviors reminiscent of ASD (see the Perspective by Estes and McAllister). A subset of T helper cells that make the cytokine interleukin-17a in the mothers caused cortical defects and associated ASD behaviors in offspring. Therapeutic targeting of interleukin-17a during gestation reduced ASD symptoms in offspring. Science, this issue p. 933; see also p. 919 Interleukin-17–producing T cells act during gestation to induce cortical and behavioral abnormalities in offspring. [Also see Perspective by Estes and McAllister] 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.
Subfields: Immunology, Obstetrics and Gynecology, Physiology
View Paper: https://www.semanticscholar.org/paper/d3e8c47c179d3263d70791b96527caa9eafdd9ac
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Citations in the corpus
- Ten questions concerning the built environment and mental health (2019, background): “This window of vulnerability for ASD risk due to environmental pollutants coincides with a critical window for development of a type of immune cell, the regulatory T cell (Treg) in the fetus, including the emergence, seeding, and expansion of Treg populations and Th17 cells (a type of immune cell th”
- The IL-17 family of cytokines in health and disease (2019, background): “Increased systemic IL-17 during pregnancy leads to development of autism-like behaviors in pup offspring (Choi et al., 2016), which can also be regulated by maternal microbiota (Kim et al.”
- Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation (2020, background): “Maternal infection or immune activation during pregnancy is another area of interest and may be a potential risk factor according to recent investigations (62-65).”
- The Changing Epidemiology of Autism Spectrum Disorders (2016, result): “These epidemiological results are consistent with animal models that demonstrate that maternal immune activation can result in autism-like phenotypes in offspring (33).”
- The Central Nervous System and the Gut Microbiome (2016, background): “Perturbation of the Microbiome and Microbial Products Can Affect Behavioral Outcomes in Mouse Models and Humans Treatment/perturbation to Microbiome Effects on Behavior Known/Presumed Mechanism (by correlation) Reference Prenatal Effects Abx offspring exhibited anxiety-like behavior and hypoactivity”