Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73


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Authors
Coppard, Valerie 
Howlett, Sarah K. 
Georgieva, Zoya 
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.

Description
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
Journal Title
Communications Biology
Conference Name
Journal ISSN
2399-3642
Volume Title
4
Publisher
Nature Publishing Group UK
Sponsorship
Wellcome Trust (Wellcome) (RG79413)