Administration of embryonic stem cell-derived thymic epithelial progenitors expressing MOG induces antigen-specific tolerance and ameliorates experimental autoimmune encephalomyelitis

•Transplantation of MOG/mESC-TEPs leads to long-lasting MOG expression in the thymus.•MOG/mESC-TEPs in the thymus induces MOG antigen-specific tolerance.•Transplantation of MOG/mESC-TEPs in mice prevents EAE development.•MOG/mESC-TEPs in mice results in long-term remission of established EAE.

Tolerance induction, and thus prevention or treatment of autoimmune disease, is not only associated with the persistent presence of self-antigen in the thymus, but also relies on a functional thymus; however, the thymus undergoes profound age-dependent involution. Thymic epithelial cells (TECs) are the major component of the thymic microenvironment for T cell development. We have reported that mouse embryonic stem cells (mESCs) can be induced in vitro to generate thymic epithelial progenitors (TEPs) that further develop into functional TECs in vivo. We show here that transplantation of mESC-TEPs expressing self-antigen myelin oligodendrocyte glycoprotein (MOG) in mice results in enhanced T cell regeneration, long-term expression of MOG in the thymus, prevention of experimental autoimmune encephalomyelitis (EAE) development, and remission of established EAE. Our findings indicate that transplantation of ESC-TEPs expressing disease-causative self-antigen(s) may provide an effective approach for the prevention and treatment of autoimmune disease.