Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children

Brain, Behavior, and Immunity

Volume 67, January 2018, Pages 335-344

AhmedNadeema

Sheikh F.Ahmada

Sabry M.Attiaa

Saleh A.Bakheeta

Naif O.Al-Harbia

Laila Y.AL-Ayadhib

aDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

bAutism Research and Treatment Center, AL-Amodi Autism Research Chair, Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Received 12 June 2017, Revised 10 September 2017, Accepted 16 September 2017, Available online 20 September 2017.

https://doi.org/10.1016/j.bbi.2017.09.010Get rights and content

Highlights

Autistic children have increased IL-17 receptor expression in monocytes.

•iNOS/nitrotyrosine expression is also higher in monocytes of autistic children.

•Activation of IL-17 receptor enhances oxidative inflammation in autistic children.

•Blockade of IL-17 receptor attenuates oxidative inflammation in autistic children.

Abstract

Millions of children are affected by different neurodevelopmental disorders, out of which autism spectrum disorder (ASD) poses a major hurdle to normal life style due to associated behavioral abnormalities. Several studies have shown an increased expression/release of Th17 related cytokine, IL-17A in ASD. IL-17A may enhance neuroinflammation via its IL-17A receptor, i.e. IL-17RA expressed in immune cells (such as monocytes) of autistic children. Increased oxidative stress has been implicated in a number of neuropsychiatric disorders including ASD. However, whether IL-17A/IL-17RA signaling contributes to oxidative inflammation in monocytes of autistic children has not been explored previously. With this background, we performed this study in peripheral monocytes of ASD patients and age-matched typically developing children. Our study shows that ASD individuals have increased IL-17RA expression in monocytes which is associated with increased nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway and inducible nitric oxide synthase (iNOS)/nitrotyrosine expression as compared to typically developing children. Moreover, in vitro activation of IL-17 receptor by IL-17A in monocytes isolated from ASD individuals leads to enhanced iNOS expression via NFκB pathway. IL-17RA antibody treatment in vitro reversed IL-17A-induced increase in NFκB and iNOS/nitrotyrosine expression in monocytes isolated from ASD subjects. These data connect increased IL-17A/IL-17RA signaling in ASD patients with enhanced oxidative inflammation in monocytes. Therefore, IL-17 receptor signaling in monocytes may potentiate the effects of IL-17A released by other immune cells and may aggravate neuroinflammation in ASD. Our study further suggests that blockade of IL-17A/IL-17 receptor signaling may be beneficial in the children with ASD.

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About S. R. Zelenz 113 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.