| First Author | Simeoni L | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 17 | Pages | 7557-68 |
| PubMed ID | 16107703 | Mgi Jnum | J:100408 |
| Mgi Id | MGI:3588459 | Doi | 10.1128/MCB.25.17.7557-7568.2005 |
| Citation | Simeoni L, et al. (2005) The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions. Mol Cell Biol 25(17):7557-68 |
| abstractText | SIT is a transmembrane adapter protein that modulates signals emanating from the T-cell receptor (TCR). Here, we have used gene-targeted mice to assess the role of SIT for T-cell development and peripheral T-cell functions. SIT(-/-) double-positive thymocytes show an upregulation of the activation markers CD5 and CD69, suggesting that SIT negatively regulates TCR-mediated signals at the CD4(+) CD8(+) stage of thymic development. This assumption is further supported by the observation that in female H-Y TCR transgenic mice, positive selection is enhanced and even converted to negative selection. Similarly, mature peripheral T cells are hyperresponsive towards TCR-mediated stimuli and produce larger amounts of T-helper 1 (TH1) cytokines, and SIT-deficient mice show an increased susceptibility to develop experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. These results demonstrate that SIT is a critical negative regulator of TCR-mediated signaling and finely tunes the signals required for thymic selection and peripheral T-cell activation. |
