| First Author | Collins S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e49801 |
| PubMed ID | 23166773 | Mgi Jnum | J:195461 |
| Mgi Id | MGI:5484501 | Doi | 10.1371/journal.pone.0049801 |
| Citation | Collins S, et al. (2012) Regulation of CD4(+) and CD8(+) effector responses by Sprouty-1. PLoS One 7(11):e49801 |
| abstractText | TCR-induced NF-AT activation leads to the expression of both activating and inhibitory proteins. Previously, we had identified Egr-2 and Egr-3 as NF-AT-induced transcription factors which promote the inhibition of T cell activation. In this report we identify Sprouty1 as a downstream target of Egr-3. CD4(+) T cells lacking Spry1 demonstrate enhanced proliferation and cytokine production. Likewise, Spry1(Flox/Flox) Lck Cre CD8(+) T cells display increased cytolytic activity. Mechanistically, Spry1 acts at the level of PLC-gamma promoting the inhibition of both Ca(+)(+) induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-kappaB signaling. In vivo, mice in which Spry1 is selectively deleted in T cells demonstrate enhanced responses to a tumor vaccine and subsequently reject tumors more robustly than Wt mice. These findings suggest that targeting Spry1 might prove to be a novel means of enhancing tumor immunotherapy. |
