PXD007574

PXD007574 is an original dataset announced via ProteomeXchange.

Title	Meningeal γδ T cells producing IL-17 control synaptic plasticity and cognitive behaviour
Description	The conventional 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 (Louveau, Trends Immunol 2015; Kipnis science 2016; Filiano, Nat Rev Neurosciences 2017). Surprisingly, such neuroimmune functions have been linked to “pro-inflammatory” cytokines like IL-4 or IFN-α, shown to control behavioural and social cognition (Derecki, JEM 2010; Filiano, Nature 2016). Here we identify a pro-cognitive role for IL-17 in short-term memory that derives from a previously unknown meningeal-resident γδ T cell subset. This was mostly composed of foetal thymic-derived Vγ6+ T cells, found in the meninges at birth and persisting throughout life, where they were strikingly polarized towards IL-17 production. In fact, γδ T cells were the overwhelming source of meningeal IL-17, whereas IFN-γ was mostly provided by T cells. To assess whether the constitutive production of IL-17 by γδ T cells influenced the cognitive performance of mice, we tested TCRδ-/-, IL-17-/- and respective WT littermate control mice in classical learning paradigms. We observed that mice deficient either for γδ T cells or IL-17 displayed impaired short-term memory in the Y maze paradigm, while retaining normal long-term spatial memory in the Morris water maze. A detailed proteomics analysis of the hippocampus provided mechanistic insight into reduced plasticity of the glutamatergic synapses in the absence of IL-17, which associated with impaired Long Term Potentiation (LTP). Conversely, IL-17 enhanced glial cell production of Brain Derived Neurotropic Factor (BDNF), whose exogenous provision rescued the LTP defect of IL-17-/- animals. Altogether, our data demonstrate that foetal-derived γδ T cells populate the brain meninges where they regulate synaptic plasticity and short-term memory through a non-inflammatory IL-17-dependent mechanism.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:02:21.933.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cátia Santa
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-28 07:32:56	ID requested
1	2019-10-16 00:10:47	announced
⏵ 2	2024-10-22 04:02:22	announced	2024-10-22: Updated project metadata.

10.1126/sciimmunol.aay5199;

Ribeiro M, Brigas HC, Temido-Ferreira M, Pousinha PA, Regen T, Santa C, Coelho JE, Marques-Morgado I, Valente CA, Omenetti S, Stockinger B, Waisman A, Manadas B, Lopes LV, Silva-Santos B, Ribot JC, T cell-derived IL-17 controls synaptic plasticity and short-term memory. Sci Immunol, 4(40):(2019) [pubmed]

curator keyword: Biological

submitter keyword: SWATH,IL-17, γδ T cells

Bruno Manadas
contact affiliation	Center for Neuroscience and Cell Biology
contact email	bmanadas@gmail.com
lab head
Cátia Santa
contact affiliation	Center for Neuroscience and Cell Biology
contact email	catiajmsanta@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/10/PXD007574

PRIDE project URI

• PRIDE
  1. PXD007574
     1. Label: PRIDE project
     2. Name: Meningeal γδ T cells producing IL-17 control synaptic plasticity and cognitive behaviour