Administration of embryonic stem cell-derived thymic epithelial progenitors expressing MOG induces antigen-specific tolerance and ameliorates experimental autoimmune encephalomyelitis. (April 2015)

• Record Type: Journal Article
• Authors: Su, Min; Song, Yinhong; He, Zhixu; Hu, Rong; Rood, Debra; Lai, Laijun
• Is Part Of: Journal of autoimmunity. Volume 58(2015)
• Page Start: 36
• Page End: 47
• Publication Date: 2015-04
• Subjects: Multiple sclerosis -- Experimental autoimmune encephalomyelitis -- Thymic epithelial cells -- Embryonic stem cells -- Tolerance induction; TECs thymic epithelial cells -- ESCs embryonic stem cells -- mESCs mouse embryonic stem cells -- TEPs thymic epithelial progenitors -- MOG myelin oligodendrocyte glycoprotein -- EAE experimental autoimmune encephalomyelitis -- Tregs regulatory T cells -- MS multiple sclerosis -- CNS central nervous system -- cTECs cortical TECs -- mTECs medullary TECs -- HSCT hematopoietic stem cell transplantation -- B6 C57BL/6J -- i.v. intravenously -- i.p. intraperitoneally -- i.t. intrathymic -- H&E hematoxylin-eosin -- LFB luxol fast blue -- BSI Bielschowski silver impregnation -- BM bone marrow -- TCD T cell-depleted -- qRT-PCR real-time quantitative reverse transcription-PCR -- CBA cytometric bead array -- PEI nonviral polyethylenimine -- DN double negative -- DP double positive -- SP single positive; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2015.01.002
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: 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.