RRC ID 67665
Author Ikeda T, Hirata S, Takamatsu K, Haruta M, Tsukamoto H, Ito T, Uchino M, Ando Y, Nagafuchi S, Nishimura Y, Senju S.
Title Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.
Journal PLoS One
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.
Volume 9(12)
Pages e115198
Published 2014-1-1
DOI 10.1371/journal.pone.0115198
PII PONE-D-14-16832
PMID 25522369
PMC PMC4270741
MeSH Animals Autoimmunity* Cell Differentiation Dendritic Cells / cytology Dendritic Cells / immunology Dendritic Cells / transplantation* Diabetes Mellitus, Type 1 / therapy* Embryonic Stem Cells / cytology* Encephalomyelitis, Autoimmune, Experimental / therapy* Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Th1 Cells / immunology*
IF 2.74
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)
Human and Animal Cells BRC5(AES0009)