Bel 10 is required for the development and suppressive function of Foxp3^(+)regulatory T cells

Foxp3^(+)regulatory T(Treg)cells play a critical role in peripheral tolerance.Bcl1O,acting as a scaffolding protein in the Carma1-Bcl10-Malt1(CBM)complex,has a critical role in TCR-induced signaling,leading to NF-kB activation and is required for T-cell activation.The role of Bcl1O in conventional T(Tconv)cells has been well characterized;however,the role of Bcl1 in the development of Treg cells and the maintenance of the suppressive function and identity of these cells has not been well characterized.In this study,we found that Bcl10 was required for not only the development but also the function of Treg cells.After deleting Bcl1O in T cells,we found that the development of Treg cells was significantly impaired.When Bcl1O was specifically deleted in mature Treg cells,the suppressive function of the Treg cells was impaired,leading to lethal autoimmunity in Bcl10^(fl/fl)Foxp3^(cre) mice.Consistently,in contrast to WT Treg cells,Bcl10-deficient Treg cells could not protect Rag1-deficient mice from T-cell transfer-induced colitis.Furthermore,Bcl1O-deficient Treg cells downregulated the expression of a series of Treg-cell effector and suppressive genes and decreased effector Treg-cell populations.Moreover,Bcl1O-deficient Treg cells were converted into IFNγ-producing proinflammatory cells with increased expression of the transcription factors T-bet and HIF-1α.Together,our study results provide genetic evidence,indicating that Bcl1O is required for the development and function of Treg cells.