The Regulating Effect And Mechanistic Investigation Of RIG-? In Controling The Development And Functional Stability Of Regulatory T Cells

Regulatory T cells play a critical role in controling of immunological tolerance and maintenance of immune homeostasis.The decreased number or functional deficiency of regulatory T cells may cause a vaiety of autoimmune diseases,redundancy of Treg cells can lead to suppression of immune response,hence ma intain the number and normal function of Treg cells will be of great significance.However,more and more recent studies show that Treg cells have considerable heterogeneity or plasticity under certain circumstances,such as in inflammatory status or lack of lymphocytes.Treg cells can acquire effector cell-like phenotype,produce some pro-inflammatory cytokines and promote the progress of inflammatory.Whereas the precise mechanism about how to maintain the stability and plasticity of Treg cells is unclear by far.In our study,we found out that Retinoid acid inducible gene I(Rig-I)has a central role in maintain the functional stability of Treg cells.Rig-I essentially maintains a functional Treg cell pool through facilitate a potential conversion of na?ve CD4⁺T to Treg cells,while inhibit the programs towards Th1 and Th17 cells,and that the deficient generation and function of Rig-I^-/-Treg cells result in more severely autoimmunological colitis.On the mechanism,we revealed that Rig-I protect the protein stability of transcription factor Foxo1 to keep the balance between Treg cells and Th1 cells.Viral RNA-unprimed Rig-I stabilizes the liable Foxo1by antagonizing Mdm2-mediated ubiquitination.O n the other hand,Rig-I also restrains Stat3 overactivation by inhibiting Jak1-mediated phosphorylation and facilitating Shp-2-mediated dephosphorylation.Thus,we demonstrate a critical homeostasis-maintaining role of Rig-I during active immunological response,independently of the classic innate immunity-triggering pathway upon viral RNA priming.Highlights:1.Rig-I is required for maintaining the homeostasis of CD4⁺T cells2.Rig-I stabilizes Foxo1 to keep the balance between Th1 and Treg cel s3.Rig-I restrains Stat3 to balance the generation between Th17 and Treg cel s4.Rig-I secures Treg cell activity independently of IPS-1-triggering pathway...