A Critical Role for Transcription Factor Smad4 in T Cell Function That is Independent of Transforming Growth Factor β Receptor Signaling

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2015 Jan 12

PMID 25577439

Citations 35

Authors

Ai-Di Gu

Song Zhang

Yunqi Wang

Hui Xiong

Thomas A Curtis

Yisong Y Wan

Affiliations

Soon will be listed here.

Abstract

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

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