Sasaki T, Takei Y. Constitutive increase of IL-17A in serum affects microglial activity in the hippocampal dentate gyrus. Jap J Biol Psych. 2021. 32(2) 154-160.
Immune responses often play an important role in the pathogenesis of neuropsychiatric disorders. 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 RORγt, a transcription factor essential for differentiation of Th17 cells (RORγt Tg mice), we examined changes in the brain caused by chronically increased IL-17A resulting from excessive activation of Th17 cells. RORγt Tg mice exhibited upregulated Rorc and Il17A mRNA expression in the colon, as well as a constitutive increase in circulating IL-17A. 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. However, GFAP+ astrocytes were unchanged in the hippocampi of RORγt Tg mice. In addition, novel object location test results indicated no difference in preference between these mice. Our findings indicate that a continuous increase of IL-17A in response to RORγt overexpression resulted in decreased microglia activity in the dentate gyrus.
Key Words: Astrocyte, Hippocampus, IL-17A, Microglia, RORγt, Th17 cells