| First Author | Park Y | Year | 2016 |
| Journal | Nat Immunol | Volume | 17 |
| Issue | 3 | Pages | 286-96 |
| PubMed ID | 26829767 | Mgi Jnum | J:259414 |
| Mgi Id | MGI:6142830 | Doi | 10.1038/ni.3352 |
| Citation | Park Y, et al. (2016) SHARPIN controls regulatory T cells by negatively modulating the T cell antigen receptor complex. Nat Immunol 17(3):286-96 |
| abstractText | SHARPIN forms a linear-ubiquitin-chain-assembly complex that promotes signaling via the transcription factor NF-kappaB. SHARPIN deficiency leads to progressive multi-organ inflammation and immune system malfunction, but how SHARPIN regulates T cell responses is unclear. Here we found that SHARPIN deficiency resulted in a substantial reduction in the number of and defective function of regulatory T cells (Treg cells). Transfer of SHARPIN-sufficient Treg cells into SHARPIN-deficient mice considerably alleviated their systemic inflammation. SHARPIN-deficient T cells displayed enhanced proximal signaling via the T cell antigen receptor (TCR) without an effect on the activation of NF-kappaB. SHARPIN conjugated with Lys63 (K63)-linked ubiquitin chains, which led to inhibition of the association of TCRzeta with the signaling kinase Zap70; this affected the generation of Treg cells. Our study therefore identifies a role for SHARPIN in TCR signaling whereby it maintains immunological homeostasis and tolerance by regulating Treg cells. |
