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PXD048248

PXD048248 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTreg cells from human blood differentiate into non-lymphoid tissue-resident effector cells upon TNFR2 costimulation
DescriptionRegulatory T (Treg) cells can facilitate transplant tolerance and attenuate autoimmune- and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg cell expansion and function in vivo and to create therapeutic Treg cell products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naïve, thymus-derived (t)Treg cells from human blood that promotes their differentiation into non-lymphoid tissue (NLT)-resident effector Treg cells, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue (LT)-resident Treg cell phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ Treg cells and conventional T (Tconv) cells, followed by bioinformatic comparison with published transcriptomic Treg cell signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminate that TNFR2 costimulation promotes Treg cell capacity for survival, migration, immunosuppression and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTreg cells. Flow cytometry validated the presence of the TNFR2-driven Treg cell signature in effector/memory Treg cells from the human placenta as opposed to blood. Thus, TNFR2 can be exploited as driver of NLT-resident Treg cell differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.
HostingRepositoryPRIDE
AnnounceDate2024-01-24
AnnouncementXMLSubmission_2024-01-24_01:39:43.911.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRayman Tjokrodirijo
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-01-04 02:57:36ID requested
12024-01-24 01:39:44announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, tTreg, Tconv, TNFR2, conventional T cell, CD28, thymus-derived regulatory T cell, Treg, regulatory T cell, costimulation
Contact List
Peter A.
contact affiliationHead Proteomics Group Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact emailP.A.van_Veelen@lumc.nl
lab head
Rayman Tjokrodirijo
contact affiliationLeiden University Medical Center, Proteomics group
contact emailR.T.N.Tjokrodirijo@lumc.nl
dataset submitter
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Dataset FTP location
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