CD70 expression determines the therapeutic efficacy of expanded human regulatory T cells.

Animals CD27 Ligand / genetics CRISPR-Associated Protein 9 CRISPR-Cas Systems Female Flow Cytometry Forkhead Transcription Factors / metabolism Gene Editing Gene Knockout Techniques Humans Mice, Inbred BALB C Sequence Analysis, RNA T-Lymphocytes, Regulatory / immunology Transcriptome Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
14 07 2020
Historique:
received: 30 10 2019
accepted: 17 06 2020
entrez: 16 7 2020
pubmed: 16 7 2020
medline: 22 6 2021
Statut: epublish

Résumé

Regulatory T cells (Tregs) are critical mediators of immune homeostasis. The co-stimulatory molecule CD27 is a marker of highly suppressive Tregs, although the role of the CD27-CD70 receptor-ligand interaction in Tregs is not clear. Here we show that after prolonged in vitro stimulation, a significant proportion of human Tregs gain stable CD70 expression while losing CD27. The expression of CD70 in expanded Tregs is associated with a profound loss of regulatory function and an unusual ability to provide CD70-directed co-stimulation to TCR-activated conventional T cells. Genetic deletion of CD70 or its blockade prevents Tregs from delivering this co-stimulatory signal, thus maintaining their regulatory activity. High resolution targeted single-cell RNA sequencing of human peripheral blood confirms the presence of CD27

Identifiants

DOI: 10.1038/s42003-020-1097-8 PMID: 32665635 PMC: PMC7360768
pubmed: 32665635
doi: 10.1038/s42003-020-1097-8
pii: 10.1038/s42003-020-1097-8
pmc: PMC7360768
doi:

Substances chimiques

CD27 Ligand 0
CD70 protein, human 0
FOXP3 protein, human 0
Forkhead Transcription Factors 0
Tumor Necrosis Factor Receptor Superfamily, Member 7 0
CRISPR-Associated Protein 9 EC 3.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

375

Subventions

Organisme : Wellcome Trust
ID : 211122/Z/18/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N027930/1
Pays : United Kingdom
Organisme : Department of Health
ID : RP-2014-05-007
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107212/A/15/Z
Pays : United Kingdom

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Auteurs

Rebeca Arroyo Hornero (R)

Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
ORCID: 0000-0001-7026-7358

Christos Georgiadis (C)

Molecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.

Peng Hua (P)

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
ORCID: 0000-0003-3774-5033

Dominik Trzupek (D)

JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK.

Li-Zhen He (LZ)

Celldex Therapeutics, Inc., Hampton, NJ, 08827, USA.

Waseem Qasim (W)

Molecular and Cellular Immunology Unit, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.

John A Todd (JA)

JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK.
ORCID: 0000-0003-2740-8148

Ricardo C Ferreira (RC)

JDRF/Wellcome Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, OX3 7BN, UK.

Kathryn J Wood (KJ)

Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.

Fadi Issa (F)

Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
ORCID: 0000-0002-8279-7732

Joanna Hester (J)

Transplantation Research and Immunology Group, Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK. joanna.hester@nds.ox.ac.uk.
ORCID: 0000-0002-7466-3849

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › CD70 expression determines the therapeutic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Antigènes CD70 › CD70 expression determines the therapeutic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées aux CRISPR › Protéine-9 associée à CRISPR › CD70 expression determines the therapeutic...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › CD70 expression determines the therapeutic...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytophotométrie › Cytométrie en flux › CD70 expression determines the therapeutic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › CD70 expression determines the therapeutic...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › CD70 expression determines the therapeutic...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-out de gènes › CD70 expression determines the therapeutic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CD70 expression determines the therapeutic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › CD70 expression determines the therapeutic...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › CD70 expression determines the therapeutic...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T régulateurs › CD70 expression determines the therapeutic...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › CD70 expression determines the therapeutic...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigènes CD27 › CD70 expression determines the therapeutic...