Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory

Meningeal γδ T cells are biased toward IL-17 production and control hippocampal synaptic plasticity and short-term memory. T cells that promote memories There is now a growing appreciation of cross-talk between the nervous and immune systems. Here, Ribeiro et al. report that interleukin-17 (IL-17)–producing γδ T cells that arise early in life and home to the meninges of neonatal mice play an essential role in the development of short-term memories. Both mice lacking γδ T cells and IL-17 show impaired performance in Y-maze tests that rely on short-term memory but did not show any deficits in other behavioral tests, including tests that gauge long-term memory. The authors found that meningeal IL-17–producing γδ T cells promote secretion of brain-derived neurotropic factor in mouse brains. Further studies are needed to understand the local and systemic effects of IL-17 on neuronal and non-neuronal cells in the brain. 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.