Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.

Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.
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表达吲哚胺 2,3-双加氧酶的主动脉浆细胞样树突状细胞通过诱导调节性 T 细胞预防动脉粥样硬化

DOI:
10.1016/j.cmet.2016.04.010
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发表时间:
2016
期刊:
影响因子:
29
通讯作者:
Cheong C
Cheong C
中科院分区:
生物学1区
文献类型:
--
作者:
Yun TJ;Lee JS;Machmach K;Shim D;Jang HS;Jung I-H;Choi J;Yoon WK;Miah MA;Bego MG;Pham TNQ;Loschko J;Krug AB;Lee S-P;Keler T;Guimond JV;Haddad E;Cohen EA;Sirois MG;El-Hamamsy I;Colonna M;Choi J-H;Cheong C

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Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren’s syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE.
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