EXPRESSION PATTERNS OF IL-17 RECEPTORS IN THE CEREBRAL CORTEX DURING POSTNATAL DEVELOPMENT AND ITS ALTERATION BY MATERNAL IMMUNE ACTIVATION

Abstract Background T-helper 17 (Th17) cells are a subset of CD4+ T cells that produce interleukin (IL)-17A. Recent studies showed that an increase in circulating IL-17A causes cognitive dysfunction, although it is unknown how increased systemic IL-17A affects brain function. Aims & Objectives Using transgenic mice overexpressing RORγ t, a transcription factor essential for differentiation of Th17 cells (RORγ t Tg mice), we examined changes in the brain caused by chronically increased IL-17A resulting from excessive activation of Th17 cells. Methods To investigate the effect of IL-17 on neuronal and glial cells in the brain, we made use of mutant mice overexpressing RORγ t (RORγ t Tg mice). Results RORγ t Tg mice exhibited elevated Rorc and IL-17A mRNA expression in the colon, as well as a chronic increase in circulating IL-17A. We found that the immunoreactivity of Iba1 and density of microglia were lower in the dentate gyrus of RORγ t Tg mice compared with wild-type mice. However, GFAP+ astrocytes were unchanged in the hippocampi of RORγ t Tg mice. Levels of synaptic proteins were not significantly different between RORγ t Tg and wild-type mouse brains. In addition, novel object location test results indicated no difference in preference between these mice. Discussion & Conclusion Our findings indicate that a continuous increase of IL-17A in response to RORγ t overexpression resulted in decreased microglia activity in the dentate gyrus, but had only a subtle effect on murine hippocampal functions. References Sasaki T, Nagata R, Takahashi S, Takei Y. Effects of RORγ t overexpression on the murine central nervous system. Neuropsychopharmacology Reports. 2021. 41(1): 102-110. Sasaki T, Tome S, Takei Y. Intraventricular IL-17A Administration Activates Microglia and Alters Their Localization in the Mouse Embryo Cerebral Cortex. Mol Brain. 13:93. 2020. Tome S, Sasaki T, Takahashi S, Takei Y. Elevated maternal retinoic acid-related orphan receptor-γ t enhances the effect of polyinosinic-polycytidylic acid in inducing fetal loss. Exp Animals. 2019. Jun 10.