The project was supervised by Prof. Bin Li in collaboration with Dr. Yu Zhang at Shanghai Jiaotong University. It was primarily executed by Ph.D. student Zhiyuan Li at the Unit of Molecular Immunology. This article reveals a new mechanism of how the immunosuppressive activity of Treg cells is modulated under inflammatory conditions. The finding provides a potential promising target to improve Treg function for treatment of autoimmune diseases, infectious diseases, allergy and tissue rejection.
FOXP3+ Treg cells play a central role in maintaining balance between tolerance and immune activation. The transcription factor FOXP3 is considered as a master regulator for the development and function of Treg cells. However, human Treg cells may be unstable and lose FOXP3 expression or convert into effector T cells under inflammatory conditions. Molecular mechanism of Treg cell instability under inflammation remains largely unclear. Protein phosphorylation is the most ubiquitous post-translational modification, and plays important role in most biological processes. Identifying site-specific phosphorylated substrates is fundamental to understand the molecular mechanisms of phosphorylation. It is attractive to study the molecular mechanism of how the activity of human Treg cells can be modulated by phosphorylation.
FIGURE: PIM1 kinase phosphorylates the human transcription factor FOXP3 at serine 422 to negatively regulate its activity A. PIM1 specific inhibitor enhances the capacity of the Treg cells to suppress the proliferation of CD8+ T cells; B. Proposed working model for the mechanism of PIM1 regulation of human FOXP3 and Treg activity.