Journal
IMMUNITY
Volume 42, Issue 1, Pages 68-79Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2014.12.019
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Funding
- NIH [R01AI097392]
- National Multiple Sclerosis Society [RG4654]
- University Cancer Research Fund
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Transforming growth factor-beta (TGF-beta) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-beta signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-beta R) deletion and compromised T-cell-mediated tumor rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and effector function, it was essential for T cell proliferation after activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-beta R-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity.
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