Effects of RORγt overexpression on the murine central nervous system

Objective 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. Using transgenic mice overexpressing ROR gamma t, a transcription factor essential for differentiation of Th17 cells (ROR gamma t Tg mice), we examined changes in the brain caused by chronically increased IL-17A resulting from excessive activation of Th17 cells. Results ROR gamma 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 ROR gamma t Tg mice compared with wild-type mice. However, GFAP(+) astrocytes were unchanged in the hippocampi of ROR gamma t Tg mice. Levels of synaptic proteins were not significantly different between ROR gamma t Tg and wild-type mouse brains. In addition, novel object location test results indicated no difference in preference between these mice. Conclusion Our findings indicate that a continuous increase of IL-17A in response to ROR gamma t overexpression resulted in decreased microglia activity in the dentate gyrus, but had only a subtle effect on murine hippocampal functions.

Automated summary

Our study found that continuous increase of IL-17A resulting from ROR gamma t overexpression led to decreased microglia activity in the dentate gyrus of the brain, but had only a subtle effect on murine hippocampal functions. The expression levels of synaptic proteins and the novel object location test results showed no significant differences between ROR gamma t Tg and wild-type mice.