Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73.
Howlett, Sarah K
Mullay, Harpreet Kaur
Van Den Bosch, Aletta
Grist, James T
Coles, Alasdair J
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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
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.
Wellcome Trust (RG79413, 105924/Z/14/Z, 220554/Z/20/Z)
External DOI: https://doi.org/10.1038/s42003-021-02721-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330831
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/