The notion of “immune privilege” of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology. However, the immune mechanisms that regulate learning and memory remain poorly understood. Here, we show that noninflammatory interleukin-17 (IL-17) derived from a previously unknown fetal-derived meningeal-resident γδ T cell subset promotes cognition. When tested in classical spatial learning paradigms, mice lacking γδ T cells or IL-17 displayed deficient short-term memory while retaining long-term memory. The plasticity of glutamatergic synapses was reduced in the absence of IL-17, resulting in impaired long-term potentiation in the hippocampus. Conversely, IL-17 enhanced glial cell production of brain-derived neurotropic factor, whose exogenous provision rescued the synaptic and behavioral phenotypes of IL-17–deficient animals. Together, our work provides previously unknown clues on the mechanisms that regulate short-term versus long-term memory and on the evolutionary and functional link between the immune and nervous systems.

对大脑的“免疫特权”的概念已经过修改，以适应稳态时参与正常神经生理学的免疫细胞对大脑的浸润。但是，调节学习和记忆的免疫机制仍然知之甚少。在这里，我们显示非炎性白细胞介素17（IL-17）源自以前未知的胎儿衍生的脑膜驻留γδT细胞亚群可促进认知。当在经典空间学习范例中进行测试时，缺少γδT细胞或IL-17的小鼠表现出不足的短期记忆，同时保留了长期记忆。在没有IL-17的情况下，谷氨酸能突触的可塑性降低，导致海马的长期增强能力受损。相反，IL-17增强了脑源性神经营养因子的神经胶质细胞产生，其外源提供拯救了IL-17缺陷动物的突触和行为表型。总之，我们的工作为调节短期记忆和长期记忆的机制以及免疫系统和神经系统之间的进化和功能联系提供了以前未知的线索。