| First Author | Beier UH | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 5 | Pages | 1022-9 |
| PubMed ID | 21199917 | Mgi Jnum | J:169179 |
| Mgi Id | MGI:4939980 | Doi | 10.1128/MCB.01206-10 |
| Citation | Beier UH, et al. (2011) Sirtuin-1 targeting promotes foxp3+ T-regulatory cell function and prolongs allograft survival. Mol Cell Biol 31(5):1022-9 |
| abstractText | Sirtuin 1 (Sirt1), a class III histone/protein deacetylase, is central to cellular metabolism, stress responses, and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation, and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4(+) T cells or Foxp3(+) Treg cells exhibited prolonged survival of major histocompatibility complex (MHC)-mismatched cardiac allografts. Allografts in Sirt1-targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3(+) Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions, and its targeting may have therapeutic value in autoimmunity and transplantation. |
