Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells

  • Klein M
  • Vaeth M
  • Scheel T
  • et al.
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Abstract

The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however, do not convert into effector T cells and regain their anergic state and suppressive activity upon proliferation. Together, these findings reveal the cAMP pathway as an attractive target for clinical intervention with Treg function.

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APA

Klein, M., Vaeth, M., Scheel, T., Grabbe, S., Baumgrass, R., Berberich-Siebelt, F., … Becker, C. (2012). Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells. The Journal of Immunology, 188(3), 1091–1097. https://doi.org/10.4049/jimmunol.1102045

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