title: Administration of embryonic stem cell-derived thymic epithelial progenitors expressing MOG induces antigen-specific tolerance and ameliorates experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA; Guiyang Medical College, Guizhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Guiyang Medical College, Guizhou, China.
authors.forename: Zhixu
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA; University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA. Electronic address: laijun.lai@uconn.edu.
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000276:immunology / Q000637:transplantation*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D004847:Epithelial Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000628:therapy*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology*; D033581:Stem Cell Transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Embryonic stem cells; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Thymic epithelial cells; Tolerance induction