Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.
Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.
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DOI：
10.1371/journal.pone.0115198
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Senju S
中科院分区：
文献类型：
--
作者：
Ikeda T;Hirata S;Takamatsu K;Haruta M;Tsukamoto H;Ito T;Uchino M;Ando Y;Nagafuchi S;Nishimura Y;Senju S
在此，我们使用两种自身免疫性疾病的模型，即非肥胖糖尿病(NOD)小鼠和实验性自身免疫性脑脊髓炎(EAE)，证明了胚胎干细胞来源的树突状细胞(ES-DC)的免疫调节作用。在超过40周的观察期内，ES-DC治疗糖尿病前期NOD小鼠几乎完全抑制了糖尿病的发展。ES-DC对糖尿病的预防作用伴随着胰岛素炎症的明显减轻和脾中Th1、Th17细胞数量的减少。ES-DC治疗也能抑制EAE的发展，即使在临床症状出现后再用ES-DC也能达到治疗效果。用ES-DC治疗EAE诱导的小鼠减少了炎症细胞对脊髓的渗透，并抑制了T细胞对髓鞘抗原的反应。重要的是，ES-DC治疗不会影响T细胞对外源抗原的反应。作为减少Th1细胞浸润的机制，我们观察到ES-DC对Th1细胞分化和增殖的抑制作用。此外，ES-DC还可显著抑制Th1细胞表面VLA-4α的表达。考虑到人类诱导多能干细胞相关技术的最新进展，这些结果表明多能干细胞来源的树突状细胞作为T细胞介导的自身免疫性疾病的治疗方法具有临床应用价值。
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.
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影响因子：
7.7
作者：
Ablamunits V;Henegariu O;Hansen JB;Opare-Addo L;Preston-Hurlburt P;Santamaria P;Mandrup-Poulsen T;Herold KC
通讯作者：
Herold KC
影响因子：
3.3
作者：
Archambault, Angela S.;Sim, Julia;Russell, John H.
通讯作者：
Russell, John H.
影响因子：
4.4
作者：
Chen, W;Bergerot, I;Delovitch, TL
通讯作者：
Delovitch, TL
影响因子：
7.7
作者：
Emamaullee JA;Davis J;Merani S;Toso C;Elliott JF;Thiesen A;Shapiro AM
通讯作者：
Shapiro AM
DOI：
10.1084/jem.191.3.435
发表时间：
2000-02-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang FP;Platt N;Wykes M;Major JR;Powell TJ;Jenkins CD;MacPherson GG
通讯作者：
MacPherson GG