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E-GEOD-26425 - Sirt1 targeting promotes Treg function

Status
Released on 5 January 2011
Organism
Mus musculus
Samples (9)
Array (1)
Protocols (6)
Description
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 and acetylation 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 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. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of Sirt1 knock out, compared to wild type (C57BL6) control
Experiment type
transcription profiling by array 
Contacts
Guanghui Ge, Liqing Wang, Rongxiang Han, Tricia R Bhatti, Ulf H Beier, Wayne W Hancock, Yujie Liu
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-26425.idf.txt
Sample and data relationshipE-GEOD-26425.sdrf.txt
Raw data (1)E-GEOD-26425.raw.1.zip
Processed data (1)E-GEOD-26425.processed.1.zip
Array designA-AFFY-36.adf.txt
R ExpressionSetE-GEOD-26425.eSet.r
Links