TIF1γ regulates stability of T regulatory cells during inflammation [RNA-seq]

Upon activation, TIF1g deficient Tregs upregulate a transcriptional profile associated with proliferation, T cell activation and T helper differentiation. Additionally, these cells acquire increased chromatin accessibility motifs for transcriptional regulators such as NFKb and different STATs; strongly suggestive of enhanced responsiveness to inflammatory cues. TIF1γ deficient Tregs show enhanced proliferation regardless TGF-β was present in the media or not; however, the T helper-like bias a Treg has in the absence of TIF1γ, occurs only in the absence of TGF-β signaling.

Finally, we identified the beta-catenin pathway as the molecular mechanism driving both TIF1γ-dependent Treg stability and proliferation upon inflammation. Unlike any other previous reports eliminating different TGF-β molecular components in Tregs, deletion of TIF1γ severely impaired Treg function and stability upon inflammation. Altogether, our data demonstrates that TIF1γ is required for the maintenance of a suppressor phenotype and stability of Treg lymphocytes during inflammatory conditions in vivo and represents a new modulatory pathway to manipulate Treg cells for therapeutic purposes.