Reversing SKI-SMAD4-mediated suppression is essential for T_H17 cell differentiation.

ABSTRACT: T helper 17 (T_H17) cells are critically involved in host defence, inflammation, and autoimmunity. Transforming growth factor β (TGFβ) is instrumental in T_H17 cell differentiation by cooperating with interleukin-6 (refs 6, 7). Yet, the mechanism by which TGFβ enables T_H17 cell differentiation remains elusive. Here we reveal that TGFβ enables T_H17 cell differentiation by reversing SKI-SMAD4-mediated suppression of the expression of the retinoic acid receptor (RAR)-related orphan receptor γt (RORγt). We found that, unlike wild-type T cells, SMAD4-deficient T cells differentiate into T_H17 cells in the absence of TGFβ signalling in a RORγt-dependent manner. Ectopic SMAD4 expression suppresses RORγt expression and T_H17 cell differ

SUBMITTER: Zhang S 

PROVIDER: S-EPMC5743442 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature