A new study has identified a subset of immune signaling proteins that are associated with the development of autism.
Blocking these proteins during pregnancy in mice eliminated autism-like behavior in offspring, hinting at a potential means to prevent development of the disorder. Increasingly, evidence suggests that alterations in a mother’s immune system – particularly in T cells and the immune signaling protein interleukin-17a (IL-17a) – during key periods of fetal neurodevelopment can lead to autism in offspring.
Gloria Choi et al. explored IL-17a in greater detail in mice. Upon mild infection 12 days into pregnancy, mothers experienced immune responses, which led to increased expression of IL-17a in the cortex of the fetus.
Analysis by the team revealed that this also led to disorganized neural connections in the cortex of the fetal brain at 18 days into gestation, and, after birth, the offspring demonstrated behaviors associated with autism.
However, this did not occur in offspring whose mothers were pretreated with a compound that blocks IL-17a. A transcription factor called RORγt is known to be a critical regulator of the IL-17a pathway, prompting Choi et al. to investigate the offspring of pregnant mothers lacking RORγt.
These mothers did not produce IL-17a upon infection, their fetuses did not develop disorganized cortexes, and after birth, their mice offspring demonstrated normal behavior.
About this Autism research
Source: Natasha Pinol – AAAS Image Source: The image is in the public domain Original Research: Abstract for “The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring” by Gloria B. Choi, Yeong S. Yim, Helen Wong, Sangdoo Kim, Hyunju Kim, Sangwon V. Kim, Charles A. Hoeffer, Dan R. Littman, and Jun R. Huh in Science. Published online January 28 2016 doi:10.1126/science.aad0314
The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring
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 γt (RORγt)–dependent effector T lymphocytes [e.g., 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.
“The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring” by Gloria B. Choi, Yeong S. Yim, Helen Wong, Sangdoo Kim, Hyunju Kim, Sangwon V. Kim, Charles A. Hoeffer, Dan R. Littman, and Jun R. Huh in Science. Published online January 28 2016 doi:10.1126/science.aad0314