Department of Cellular Neurobiology, Zoological Institute, Braunschweig, Germany.
Neuroinflammation and Neurodegeneration Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Elife. 2022 Aug 30;11:e75889. doi: 10.7554/eLife.75889.
The anti-inflammatory cytokine interleukin-37 (IL-37) belongs to the IL-1 family but is not expressed in mice. We used a human IL-37 (hIL-37tg) expressing mouse, which has been subjected to various models of local and systemic inflammation as well as immunological challenges. Previous studies reveal an immunomodulatory role of IL-37, which can be characterized as an important suppressor of innate immunity. Here, we examined the functions of IL-37 in the central nervous system and explored the effects of IL-37 on neuronal architecture and function, microglial phenotype, cytokine production and behavior after inflammatory challenge by intraperitoneal LPS-injection. In wild-type mice, decreased spine density, activated microglial phenotype and impaired long-term potentiation (LTP) were observed after LPS injection, whereas hIL-37tg mice showed no impairment. In addition, we crossed the hIL-37tg mouse with an animal model of Alzheimer's disease (APP/PS1) to investigate the anti-inflammatory properties of IL-37 under chronic neuroinflammatory conditions. Our results show that expression of IL-37 is able to limit inflammation in the brain after acute inflammatory events and prevent loss of cognitive abilities in a mouse model of AD.
抗炎细胞因子白细胞介素-37（IL-37）属于白细胞介素 1 家族，但在小鼠中不表达。我们使用了一种表达人白细胞介素 37（hIL-37tg）的小鼠，该小鼠已经经历了各种局部和全身炎症模型以及免疫挑战。先前的研究揭示了 IL-37 的免疫调节作用，可将其特征化为先天免疫的重要抑制剂。在这里，我们研究了 IL-37 在中枢神经系统中的功能，并探讨了 IL-37 在炎症挑战后对神经元结构和功能、小胶质细胞表型、细胞因子产生和行为的影响，方法是通过腹腔内注射 LPS。在野生型小鼠中，LPS 注射后观察到棘突密度降低、小胶质细胞激活表型和长时程增强（LTP）受损，而 hIL-37tg 小鼠则没有受损。此外，我们将 hIL-37tg 小鼠与阿尔茨海默病（APP/PS1）动物模型进行了杂交，以研究 IL-37 在慢性神经炎症条件下的抗炎特性。我们的结果表明，IL-37 的表达能够限制急性炎症事件后大脑中的炎症，并防止 AD 小鼠模型认知能力的丧失。
