Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73
Authors
Coppard, Valerie
Howlett, Sarah K.
Georgieva, Zoya
Mullay, Harpreet Kaur
Ashmore, Tom
Van Den Bosch, Aletta
Grist, James T.
Coles, Alasdair J.
Mousa, Hani S.
Peruzzotti-Jametti, Luca
Publication Date
2021-10-14Journal Title
Communications Biology
Publisher
Nature Publishing Group UK
Volume
4
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Jarvis, L. B., Rainbow, D. B., Coppard, V., Howlett, S. K., Georgieva, Z., Davies, J. L., Mullay, H. K., et al. (2021). Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73. Communications Biology, 4 (1) https://doi.org/10.1038/s42003-021-02721-x
Abstract
Abstract: 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.
Keywords
Article, /631/250/24/1529, /631/250/24/1313, /631/250/1619/554/1898/1271, /631/250/251/1574, /13/1, /13/31, /13/106, /38/39, /82, /82/58, /64/60, /13/21, article
Sponsorship
Wellcome Trust (Wellcome) (RG79413)
Identifiers
s42003-021-02721-x, 2721
External DOI: https://doi.org/10.1038/s42003-021-02721-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329476
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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