Title |
Regulation of CD4+ and CD8+ Effector Responses by Sprouty-1
|
---|---|
Published in |
PLOS ONE, November 2012
|
DOI | 10.1371/journal.pone.0049801 |
Pubmed ID | |
Authors |
Sam Collins, Adam Waickman, Albert Basson, Abraham Kupfer, Jonathan D. Licht, Maureen R. Horton, Jonathan D. Powell |
Abstract |
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-γ promoting the inhibition of both Ca⁺⁺ induced NF-AT activation and MAP-kinase induced AP-1 activation while sparing NF-κB 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. |
Mendeley readers
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 16% |
Researcher | 4 | 13% |
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Psychology | 1 | 3% |
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