| First Author | Klein M | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 3 | Pages | 1091-7 |
| PubMed ID | 22190184 | Mgi Jnum | J:180768 |
| Mgi Id | MGI:5307192 | Doi | 10.4049/jimmunol.1102045 |
| Citation | Klein M, et al. (2012) Repression of cyclic adenosine monophosphate upregulation disarms and expands human regulatory T cells. J Immunol 188(3):1091-7 |
| abstractText | 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/alphaA. 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. |
