Remarks for the authors: Sasaki and colleagues describe detailed microglial changes related to autism spectrum disorder (ASD). They employed interleukin 17 (IL-17) because previous report has demonstrated that the maternal immune activation by IL-17 causes structural and behavioral changes relating ASD. During this process, previous pharmacological studies have implicated possible roles of microglia. The authors in the present study demonstrated that the intraventricular IL-17A administration induced accumulation of microglia to the medial cortex. They further demonstrated that microglia changed their morphology into amoeboid shape with up-regulation in CD68. Because the total Iba1-positive microglial cell number was not different, they seemed to accumulate to the specific brain area via chemotaxis. This study suggests that microglial special and functional changes during developmental stage may cause specific brain function. I have a few concerns that need to be discussed.

・The authors showed that IL-17 injection caused microglial accumulation to the cingulate cortex. Is there any known or possible mechanisms? ・In many cases, microglial activation accompany with cell proliferation. In the present study, the authors demonstrated IL-17 induced amoeboid-like changes without cell proliferation. Is such reaction specific for IL-17? ・IL-17 induced microglial accumulation. Is such chemotaxis triggered by IL-17RA in microglia? Or, IL-17 triggers other mechanisms such as purinergic system (i.e. P2Y12)? ・Related to the former comment, why microglia accumulate to the specific brain area and show phagocytic activity? Neurons release ‘find-me’ (Chekeni et al. Nature 2010) and ‘eat-me’ signals (Koizumi et al. Nature 2007). Is it possible to evoke these signals by IL-17? ・Microglia during development express neurotrophic factor to support neural survival (Ueno et al. Nat Neurosci 2017). The ASD-induction mechanism by IL-17 may be in part by loss of neurotrophic support by microglia? ・One attractive hypothesis for ASD is E/I balance hypothesis. Does aberrant microglial phagocytosis target specific type of neurons such as inhibitory neurons?