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.