SKI-dependent TGFb signaling dictates CD103 expression in CD8+ T cells (ChIP-seq)

Initially identified as a functional marker for resident-memory (Trm) CD8+ T cells, CD103 (encoded by ITGAE gene) has broad roles in immunity and diseases. Elucidating the function and regulation of CD103 is thus of importance. This study revealed that the CD103 expression by CD8 T cells under steady state contributes to the clearance of acute viral infection. More importantly, it discovered TGF?-SKI-Smad4 a critical signaling axis in restricting CD103 expression in CD8+ T cells for their function. Mechanistically, by ChIP-Seq and ChIP analysis, SKI associated with Smad4 was found to directly and epigenetically suppress CD103 transcription. This study therefore reveals a novel TGF?-SKI-Smad4 pathway to specifically enable CD103 expression in CD8+ T cells for protective immunity. Overall design: Examination of Smad4 and Ski ChIP-seq in two different cells (WT vs. Cd4Cre;Smad4fl/fl) under TGFbR inhibitor condition for 2 days