Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
14 10 2021
14 10 2021
Historique:
received:
17
11
2020
accepted:
27
09
2021
entrez:
15
10
2021
pubmed:
16
10
2021
medline:
21
12
2021
Statut:
epublish
Résumé
The adoptive transfer of regulatory T-cells (Tregs) is a promising therapeutic approach in transplantation and autoimmunity. However, because large cell numbers are needed to achieve a therapeutic effect, in vitro expansion is required. By comparing their function, phenotype and transcriptomic profile against ex vivo Tregs, we demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A) driven acquisition of CD73 expression. In conjunction with CD39, CD73 expression enables expanded Tregs to convert ATP to immunosuppressive adenosine. We conclude that for maximum therapeutic benefit, Treg expansion protocols should be optimised for CD39/CD73 co-expression.
Identifiants
pubmed: 34650224
doi: 10.1038/s42003-021-02721-x
pii: 10.1038/s42003-021-02721-x
pmc: PMC8516976
doi:
Substances chimiques
GPI-Linked Proteins
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
5'-Nucleotidase
EC 3.1.3.5
NT5E protein, human
EC 3.1.3.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1186Subventions
Organisme : Wellcome Trust (Wellcome)
ID : RG79413
Organisme : Wellcome Trust
ID : 105924/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211122/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107212/A/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011705/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N027930/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A090_1006
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011705/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220554/Z/20/Z
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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