Abstract
We herein demonstrate the immune-regulatory effect of embryonic stem cell-derived dendritic cells (ES-DCs) using two models of autoimmune disease, namely non-obese diabetic (NOD) mice and experimental autoimmune encephalomyelitis (EAE). Treatment of pre-diabetic NOD mice with ES-DCs exerted almost complete suppression of diabetes development during the observation period for more than 40 weeks. The prevention of diabetes by ES-DCs was accompanied with significant reduction of insulitis and decreased number of Th1 and Th17 cells in the spleen. Development of EAE was also inhibited by the treatment with ES-DCs, and the therapeutic effect was obtained even if ES-DCs were administrated after the onset of clinical symptoms. Treatment of EAE-induced mice with ES-DCs reduced the infiltration of inflammatory cells into the spinal cord and suppressed the T cell response to the myelin antigen. Importantly, the ES-DC treatment did not affect T cell response to an exogenous antigen. As the mechanisms underlying the reduction of the number of infiltrating Th1 cells, we observed the inhibition of differentiation and proliferation of Th1 cells by ES-DCs. Furthermore, the expression of VLA-4α on Th1 cells was significantly inhibited by ES-DCs. Considering the recent advances in human induced pluripotent stem cell-related technologies, these results suggest a clinical application for pluripotent stem cell-derived dendritic cells as a therapy for T cell-mediated autoimmune diseases.
Highlights
Autoimmune diseases occur and develop when immunological self-tolerance is broken by some mechanisms and autoreactive lymphocytes attack tissues [1]
As various auto-antigens are etiologically involved in human autoimmunity, we investigated the preventive effects of genetically modified embryonic stem cellderived dendritic cells (ES-Dendritic cells (DCs)) in another autoimmune model: non-obese diabetic (NOD) mice
We previously showed that genetically modified embryonic stem (ES)-DCs inhibit the onset of the EAE, a model of autoimmune disease induced by immunization with a specific myelin auto-antigen [22]
Summary
Autoimmune diseases occur and develop when immunological self-tolerance is broken by some mechanisms and autoreactive lymphocytes attack tissues [1]. Therapeutic drugs including corticosteroids, other immune suppressants, and molecularly targeted drugs are effectively used for the treatment of some autoimmune diseases, long-term administration of these drugs increases the risk of systemic immune suppression and consequent opportunistic infections or the development of cancer [2, 3]. It would be greatly advantageous if we could develop a therapeutic means of inhibiting autoimmunity while preserving immunity against exogenous pathogens. Some animal models of autoimmune diseases were prevented by the transfer of modulated DCs [14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
