Journal Club (October 4, 2021)

SCIENCE IMMUNOLOGY 11 Oct 2019 Vol 4, Issue 40 DOI: 10.1126/sciimmunol.aay5199

RESEARCH ARTICLENEUROIMMUNOLOGY

Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory (髄膜γδT細胞由来のIL-17は、シナプス可塑性と短期記憶を制御する)

Miguel Ribeiro 1, Helena C Brigas 1, Mariana Temido-Ferreira 1, Paula A Pousinha 2, Tommy Regen 3, Cátia Santa 4 5, Joana E Coelho 1, Inês Marques-Morgado 1, Cláudia A Valente 1, Sara Omenetti 6, Brigitta Stockinger 6, Ari Waisman 3, Bruno Manadas 4, Luísa V Lopes 1, Bruno Silva-Santos

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

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.

Abstract
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.

Foetal derived γδ T cells infiltrate the meninges from birth.Meningeal cell suspensions were prepared from 8-20 weeks-old C57BL/6J WT and Il17aCre R26ReYFP mice (A-B; D-E), 0-52 weeks-old C57BL/6J WT mice (C), and 20 weeks-old WT and WT → WT bone marrow chimeras (BMC) mice (G). Samples were analysed for the expression of indicated surface (CD45, CD3, TCRδ, CD4, CD8, Vγ1, Vγ4, Vγ5, Vγ6, CD27 and CCR6) and intracellular (RORgt, Tbet, IL-17 and IFN-γ) markers. Live cells were gated using LiveDead Fixable Viability Dye as shown in A. Dot plots represents cell populations from indicated gates. Histograms depicts percentages or absolute numbers from indicated populations. Meningeal spaces were pooled from 4 mice. Spleens were analysed from individual mice. Results are representative of 4-7 independent experiments. Error bars, mean + s.e.m. * P<0.05, **P<0.01, ***P<0.001 as calculated by student T-test (parametric) or Mann-Whitney test (non parametric).

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