Tolerogenic dendritic cells are efficiently generated using minocycline and dexamethasone.
Tolerogenic dendritic cells are efficiently generated using minocycline and dexamethasone.
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DOI：
10.1038/s41598-017-15569-1
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发表时间：
2017-11-08
影响因子：
4.6
通讯作者：
Lee CK
中科院分区：
文献类型：
--
作者：
Lee JH;Park CS;Jang S;Kim JW;Kim SH;Song S;Kim K;Lee CK
耐受性树突状细胞(TDCs)是治疗自身免疫性疾病、过敏和移植排斥反应的一种很有前途的细胞治疗工具。已知许多药理药物可诱导TDC的产生。米诺环素长期以来一直被用作广谱抗生素，最近被证明可以显著增加具有调节特性的DC的生成。在这里，我们研究了米诺环素与地塞米松、雷帕霉素、维生素D3和白介素10的联合作用，这些都是已知的TDC产生的诱导剂。当米诺环素、地塞米松与粒细胞集落刺激因子(GM-SCF)、IL-4联合使用时，tDCs数量最多。体外表型和功能测定表明，米诺环素/地塞米松处理的tDCs的耐受性远好于或至少等于这两种药物所产生的tDCs。此外，MOG35-55多肽冲击的米诺环素/地塞米松调节的tDCs可显著改善MOG多肽注射所致的小鼠实验性自身免疫性脑炎的临床体征。这些结果证实了米诺环素、地塞米松、GM-CSF和IL-4联合使用可以有效地产生具有强大耐受性的tDCs。我们的研究结果将有助于开发基于TDC的体外免疫疗法。
Tolerogenic dendritic cells (tDCs) represent a promising tool for cellular therapy against autoimmune diseases, allergies, and transplantation rejection. Numerous pharmacological agents are known to induce tDC generation. Minocycline, which has long been used as a broad-spectrum antibiotic, was recently shown to significantly increase the generation of DCs with regulatory properties. Here, we examined the effect of the combination of minocycline with dexamethasone, rapamycin, vitamin D3, and interleukin (IL)-10, which are all known inducers of tDC generation. The highest number of tDCs was generated when minocycline and dexamethasone were used together with granulocyte colony-stimulating factor (GM-SCF) and IL-4. The tolerogenicity of the minocycline/dexamethasone-conditioned tDCs was much better than or at least equal to those of the tDCs generated with either one of these agents, as assessed through in vitro phenotypic and functional assays. In addition, pretreatment with MOG35-55 peptide-pulsed minocycline/dexamethasone-conditioned tDCs significantly ameliorated the clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection in a murine model. These results confirmed that tDCs with potent tolerogenic properties could be efficiently generated by the combined use of minocycline and dexamethasone, along with GM-CSF and IL-4. Our results would help in the development of ex vivo tDC-based immunotherapies.
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通讯作者：
ten Brinke, Anja
影响因子：
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作者：
Kim N;Park CS;Im SA;Kim JW;Lee JH;Park YJ;Song S;Lee CK
通讯作者：
Lee CK
影响因子：
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作者：
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通讯作者：
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