ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms

Min Su; Yujun Lin; Cheng Cui; Xiaohong Tian; Xiuling Lu; Zhixu He; Laijun Lai

doi:10.1016/j.cellimm.2017.10.007

ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and peripheral tolerance mechanisms

Cell Immunol. 2017 Dec:322:84-91. doi: 10.1016/j.cellimm.2017.10.007. Epub 2017 Oct 18.

Authors

Min Su¹, Yujun Lin², Cheng Cui², Xiaohong Tian², Xiuling Lu³, Zhixu He⁴, Laijun Lai⁵

Affiliations

¹ Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA; Tissue Engineering and Stem Cell Research Center, School of Basic Medical Sciences, Guizhou Medical University, Guizhou, China.
² Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
³ Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.
⁴ Tissue Engineering and Stem Cell Research Center, School of Basic Medical Sciences, Guizhou Medical University, Guizhou, China; Pediatric Department of the Affiliated Hospital, Guizhou Medical University, Guizhou, China. Electronic address: hzx@gmc.edu.cn.
⁵ 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.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), and is induced by immunization with disease-causative self-antigens such as myelin oligodendrocyte glycoprotein (MOG). We have previously reported that transplantation of MOG expressing thymic epithelial progenitors (TEPs) derived from 129S6SvEv Tac mouse embryonic stem cells (mESCs) prevented the development of EAE. In this study, we expand our previous studies to show that transplantation of MOG expressing mESC-TEPs derived from C57BL/6 mice also prevents EAE development. Furthermore, by using a MOG-specific T cell receptor (TCR) transgenic mouse model, we demonstrate that both central and peripheral tolerances are involved in the prevention of EAE induced by MOG expressing mESC-TEPs. Our results suggest that transplantation of human ESC-TEPs expressing MOG may provide an effective approach for the induction of MOG-specific immune tolerance, thereby the prevention and treatment of MS.

Keywords: Embryonic stem cells; Experimental autoimmune encephalomyelitis; Multiple sclerosis; T cells; Thymic epithelial cells; Tolerance induction.

MeSH terms

Animals
Disease Models, Animal
Embryonic Stem Cells / metabolism*
Embryonic Stem Cells / transplantation*
Encephalomyelitis, Autoimmune, Experimental / immunology
Encephalomyelitis, Autoimmune, Experimental / prevention & control*
Epithelial Cells / metabolism*
Epithelial Cells / transplantation*
Humans
Immune Tolerance / immunology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Multiple Sclerosis / prevention & control
Multiple Sclerosis / therapy
Myelin-Oligodendrocyte Glycoprotein / biosynthesis*
Myelin-Oligodendrocyte Glycoprotein / immunology
Receptors, Antigen, T-Cell / metabolism
Thymus Gland / cytology

Substances

Mog protein, mouse
Myelin-Oligodendrocyte Glycoprotein
Receptors, Antigen, T-Cell

Grants and funding

R01 AI123131/AI/NIAID NIH HHS/United States