Control Of Th17/Tregs Balance By Yes-Associated Protein

Background:T cells differentiation into distinct functional effector and inhibitory subsets is regulated by the transcriptional factor,cytokines and other regulators at the time of antigen recognition.However,the molecular mechanism how to regulate the differentiation of regulatory T cells(Treg)and Th17 cells in many autoimmune diseases remain ill-defined,especially in autoimmune diseases and post-transplant rejection.Yes-associated protein(YAP)is the major of downstream effector of the Hippo pathway,which regulates tissue homeostasis,organ size,regeneration and tumorigenesis.Currently,many studies have gradually demonstrated the biological function and mechanism controlling cancer progress.Control of Th17/Treg Balance by YAP is unclear before we share here that the deletion of YAP in Treg resulted in the defective generation and function of Treg.Objective:To investigate the expression of YAP in distinct T cells s subsets at the time of antigen recognition and the influence of YAP on the differentiation and function of regulatory T cells and Th17 cells.Methods:To determine the expression of YAP in different CD4+T cells subsets differentiated by CD4+Naive T cells using the real-time PCR.To verify the influence of the deficiency of YAP on the induction of in vitro Treg and Th17 cells.Using the in vitro suppression assay to demonstrate the effect of the deficiency of YAP in the function of Treg cells.To clarify whether the overexpression of YAP has influence on the expression of IL-17 gene through using the luciferase assay.Finally,we used EAE(Experimental autoimmune encephalomyelitis)model to determine whether the deficiency of YAP could promote the progression of this disease and decrease of the viability of this disease.Results:Our results shown that the expression of YAP had been specifically enhanced in Treg cells,the in vitro differentiation and function of Treg cells has been decreased by the deficiency of YAP.Meanwhile,the differentiation of Th17 and the expression of IL-17A and transcription factor RORyt have been increased in the same condition.We determined the role of YAP in the function of Treg cells in vivo EAE model,where the progression and mobility have been increased by the deficiency of YAP.Conclusions:YAP has played a pivotal role in the regulation of the balance between Tre and Th17 cells.We hope that our findings can able to be useful in the treatment of autoimmune diseases and immune rejection after transplantation.