Egress of murine regulatory T cells from the thymus requires TIPE2

Regulatory T cells (Tregs) can be divided into thymus-derived Treg (tTregs) and peripheral induced Tregs (pTregs) in vivo according to their origins and are essential for the maintenance of immune hemostasis and immune tolerance. Tumor necrosis factor-α-induced protein 8 like 2 (TIPE2) is expressed primarily by immune cells and is a negative regulator of the innate and adaptive immune response. Previous studies indicate that TIPE2 is required for the expression of Treg signature genes and promotes leading-edge formation in neutrophils through cytoskeleton remodeling. In the current study, we showed that TIPE2 deficient mice accumulate more Treg cells in the thymus. Further studies revealed that TIPE2 deficiency doesn't affect the development and apoptosis of tTregs. Instead, TIPE2 promotes the chemotaxis of tTregs in vitro, which may account for the accumulation of Tregs in the thymus of TIPE2 deficient mice. Mechanistic study revealed that TIPE2 promotes the polarization of pAKT and F-actin in tTregs undergoing directed migration. Taken together, these results demonstrated that TIPE2 enhances the cytoskeleton remodeling and promotes the thymus egress of tTregs, which may play an important role in the maintenance of self-tolerance.