以下の総説が発行されました。

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. 

Abstract

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.

ヘルパーT細胞サブセットであるTh17細胞による免疫反応は、自閉スペクトラム症、統合失調症、うつ病などの病態生理に関与することが臨床研究から示されている。これらの疾患では中枢神経系の構造異常がみられるが、Th17細胞とIL-１７Aの寄与については不明である。本研究では、血清中のIL-17A濃度が恒常的高値を示す遺伝子改変動物の脳の解析を行い、海馬歯状回でミクログリア活性状態の低下と密度の減少を見出した。

Key Words: Astrocyte, Hippocampus, IL-17A, Microglia, RORγt, Th17 cells