Roles of immune molecules in the formation of the cerebral cortex and their abnormalities in psychiatric disorders

Abstract

Immune responses play important roles in the pathogenesis of neuropsychiatric disorders. Recent studies showed that an increase in circulating interleukin (IL)-17A causes cognitive dysfunction, although it is unknown how increased systemic IL-17A affects brain function. Using transgenic mice overexpressing RORγt, a transcription factor essential for differentiation of Th17 cells, we examined changes in the brain caused by chronically increased IL-17A resulting from excessive activation of Th17 cells. We found that the immunoreactivity of Iba1 and density of Iba1+ microglia were lower in the dentate gyrus of RORγt Tg mice compared with wild-type mice. The immune response by Th17 cells not only directly affects the brain of the individual concerned, but has also been shown to affect the next generation. It is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we performed direct administration of IL-17A into the lateral ventricles of fetal mouse brain. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data suggest that IL-17A activates cortical microglia, which could lead to a series of ASD-related brain pathology, including excessive phagocytosis of neural progenitor cells in the ventricular zone.