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The Maternal Interleukin-17a Pathway in Mice Promotes Autism-like Phenotypes in Offspring
Objectives: Based on previous observations suggesting their involvement in ASD, we tested whether TH17 cell population and its cytokine are necessary for MIA phenotypes.
Methods: N/A
Results: Using both genetic mutants and blocking antibodies targeting their activities, we have recently found that Th17 cells are critical mediators working in pregnant mice to induce behavioral abnormalities in MIA-affected offspring. T cell-specific inactivation of RORgt 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 maternal inflammation leads to abnormal cortical phenotypes in offspring and this malformation is fully rescued by inhibiting the maternal IL-17a pathway. We also found that the receptor for IL-17 (IL-17R) is expressed in the developing fetal brain and its expression is increased in the cortex upon MIA.
Conclusions: These observations suggest a hypothesis that uncontrolled activation of IL-17R expressed in fetal brain induces abnormal cortical development and these structural abnormalities may be an underlying cause of the MIA-dependent behavioral phenotypes.