A critical role for transcription factor Smad4 in T cell function that is independent of transforming growth factor ? receptor signaling.

ABSTRACT: Transforming growth factor-beta (TGF-?) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-? 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-?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-?R-independent role for Smad4 in promoting T cell function, autoimmunity, and anti-tumor immunity.

SUBMITTER: Gu AD 

PROVIDER: S-EPMC4303504 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature