Fine-tuning the balance of mucosal immunity by protein phosphatase 4

The gut micro-environment is maintained by balancing inflammatory responses, which drive off the pathogens, and immune suppressions, which prevent tissue damages.  This balance is kept through the complex interactions between innate, adaptive, and innate-like immune cells.  Results from mouse models suggest that Treg cells play an important role in this process by negatively regulating the activities of many cell types.  Our recent report showed that protein phosphatase 4 (PP4) is essential for Treg homeostasis, homing, and functions; moreover, T-cell-specific ablation of PP4 resulted in the onset of spontaneous rectal prolapse and colitis.  Here, we demonstrated that PP4 ablation also caused severe defects in T cell proliferation and adaptive immunity.   These defects resulted from a partial G1-S block in activated PP4-deficient T cells, and were further associated with altered ROS induction and AMPK activation.  These data provide an additional perspective to suggest that, in addition to Treg defects, defective T cell responses may also contribute to the spontaneous colitis in mice with T cell-specific ablation of PP4.