Maternal IL-17A in autism.
1Institute for Behavioral Genetics, University of Colorado-Boulder, CO 80303, United States; Department of Integrative Physiology, University of Colorado-Boulder, Boulder, CO 80303, United States; Linda Crnic Institute, University of Colorado-Anschutz Medical Campus, Aurora, CO 80045, United States.
Experimental Neurology
|April 30, 2017
Summary
Maternal immune activation during pregnancy may lead to autism spectrum disorder (ASD) in offspring via inflammation. Targeting interleukin-17A (IL-17A) signaling may prevent ASD-like behaviors and cortical dysplasia.
Area of Science:
- Neuroimmunology
- Developmental Neuroscience
- Immunology
Background:
- Autism spectrum disorder (ASD) has complex etiology involving genetic and environmental factors.
- Immune dysregulation, including maternal immune activation (MIA), is increasingly recognized as a risk factor for ASD.
- Elevated levels of interleukin-17A (IL-17A) are observed in some individuals with ASD and in MIA animal models.
Purpose of the Study:
- To investigate the role of T helper 17 (Th17) cells and IL-17A in the pathogenesis of ASD following MIA.
- To explore the potential of targeting IL-17A signaling as a therapeutic strategy for MIA-associated ASD.
Main Methods:
- Utilized a mouse model of MIA to study offspring neurodevelopment and behavior.
- Administered antibody blockade to inhibit IL-17A signaling in pregnant mice.
- Genetically inhibited Th17 cell differentiation using RORγt knockout in pregnant mice.
Main Results:
- MIA exposure in mice resulted in offspring with ASD-like behaviors and cortical dysplasia.
- Inhibition of IL-17A signaling prevented ASD-like behaviors and cortical abnormalities in offspring.
- Blocking Th17 cell differentiation in pregnant mice also prevented these outcomes.
Conclusions:
- IL-17A dysregulation, driven by maternal Th17 cells, plays a causal role in MIA-associated ASD.
- IL-17A signaling impacts neural development, potentially explaining cognitive and behavioral deficits in ASD.
- Targeting the IL-17A pathway presents a potential therapeutic avenue for preventing ASD development following maternal inflammation.
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