Characterizing the adhesive properties of cytokine receptor IL17Ra during brain development
Year: 2016
Type: article
Abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that is mainly characterized by three different deficits -social behavior, communication, and characteristic repetitive behaviors.Many human studies revealed the significant effect of environmentally-induced maternal immune activation (MIA) during pregnancy in the pathogenesis of ASD, especially in genetically vulnerable individuals.This observation has been modeled in MIA rodents to better understand the neural basis of MIA-induced ASD deficits.Although many studies have hinted at the importance of the T helper 17 (Th17) cell pathway in the pathogenesis of ASD, the exact immune cell populations responsible for inducing ASD-like phenotypes in MIA animal models have not been identified.A recent study revealed that interleukin-17a (IL-17a), the effector cytokine of Th17 cells, is a critical regulator of neurodevelopment, thus suggesting the importance of its receptor IL17Ra in causing ASD-like phenotypes in the MIA models as well.In this study, we aimed to characterize the role of the cytokine receptor IL17Ra in various neurodevelopmental processes.We had hypothesized that the protein potentially acts as a cell adhesion molecule to critically regulate the cellular phenotypes during cell adhesion, neurite outgrowth, and synapse formation.Contrary to our hypothesis, we demonstrated that IL17Ra inhibits, rather than stimulates, cell adhesion, as cell adhesion levels of IL17Ra-overexpressing non-neuronal cells were lower than those of control cells.IL17Ra expression in wild type primary cortical neurons also suppressed neurite outgrowth and synapse puncta formation, further supporting the inhibitory role of the protein.Possible mechanisms by which IL17Ra is involved in neurodevelopment and the implications will be discussed.Further elucidation of the role of IL17Ra could lead to more definitive therapeutic and preventative tools for ASD, as targeting of Th17 cells in conjunction with regulating IL17Ra expression in susceptible pregnant mothers may allow us to reduce the likelihood of bearing children with inflammation-induced ASD phenotypes.
Author: Ashley Park
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2411317698