The Role Of Ddb1 In Suppressive Activity And Stability Maintenance Of Regulatory T Cells

Regulatory T cells(Treg cells)play an essential role in the immunological suppression to maintain immune homeostasis.The dysfunction of Treg cells always causes autoimmune disease.Recently,more and more studies are focused on the vital role of metabolic balance in control of Treg cell stability.Although damage-specific DNA binding protein 1(Ddb1)has been identified as a positive regulator to support cell proliferation by promoting cell cycle progress,its role in Treg cells remains to be explored.In this study,we reported that Ddb1 not only promoted Treg cell proliferation,but also maintained the metabolic balance in Treg cells.Treg-specific deletion of Ddb1 led to early-onset fatal systemic autoimmune disease in mice with excessive activation of peripheral effector T cells.In a steady environment without inflammation,Ddb1-deficient Treg cells exhibited normal development in the thymus and intact homeostasis in the periphery.However,the expression of functional molecules was declined obviously in Ddb1-deficient Treg cells.Further investigation revealed that Ddb1 deficiency in Treg cells resulted in loss of suppressive activity,due to the unrestrained glycolysis and increased level of ROS,a by-product generated along with enhanced mitochondrial metabolism and OXPHOS.Moreover,the protein level of p53 was elevated in Ddb1-deficient Treg cells after activation.Consequently,the proliferation of Ddb1 deficient Treg cells after activation was impaired due to defective cell cycle entry.Therefore,our study suggests that Ddb1 is indispensable for the proliferation and suppressive activity of Treg cells after activation.