T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor-β (TGF-β). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-κB family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.
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|---|---|
| rdf:type | |
| rdfs:comment |
T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor-β (TGF-β). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-κB family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.
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| skos:exactMatch | |
| uniprot:name |
Nat. Immunol.
|
| uniprot:author |
Brittain G.C.,
Chang J.H.,
Chang M.,
Cheng X.,
Hwu P.,
Jin W.,
Li P.,
Rabinovich B.A.,
Sun S.C.,
Wang Y.H.,
Xiao Y.,
Yu J.,
Zhou X.
|
| uniprot:date |
2011
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| uniprot:pages |
1002-1009
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| uniprot:title |
The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity.
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| uniprot:volume |
12
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| dc-term:identifier |
doi:10.1038/ni.2090
|