Minocycline promotes the generation of dendritic cells with regulatory properties.
Minocycline promotes the generation of dendritic cells with regulatory properties.
复制标题
DOI：
10.18632/oncotarget.10810
复制
发表时间：
2016-08-16
期刊：
影响因子：
--
通讯作者：
Lee CK
中科院分区：
文献类型：
--
作者：
Kim N;Park CS;Im SA;Kim JW;Lee JH;Park YJ;Song S;Lee CK
米诺环素长期以来一直被用作广谱抗生素，也表现出非抗生素性质，如抑制炎症和血管生成。在这项研究中，我们表明，米诺环素显着增强树突状细胞（DC）的产生从小鼠骨髓（BM）细胞时，与GM-CSF和IL-4一起使用。在米诺环素存在下由BM细胞产生的DC（Mino-DC）显示出调节性DC的特征。与对照DC相比，Mino-DC对随后的成熟刺激具有抗性，在MHC II类限制性外源性Ag呈递中受损，并且显示出细胞因子分泌减少。Mino-DCs还显示出降低的引发同种异体特异性T细胞的能力，同时在体外和体内增加CD 4 + CD 25 + Foxp 3 + T调节细胞的扩增。此外，用MOG 35 -55肽脉冲的Mino-DC预处理改善了由MOG肽注射诱导的实验性自身免疫性脑炎的临床体征。我们的研究将米诺环素确定为一种新的药理学药物，可能用于增加调节性DC的产生，用于细胞治疗，以治疗自身免疫性疾病，过敏和移植排斥。
Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse bone marrow (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion. Mino-DCs also show decreased ability to prime allogeneic-specific T cells, while increasing the expansion of CD4+CD25+Foxp3+ T regulatory cells both in vitro and in vivo. In addition, pretreatment with MOG35-55 peptide-pulsed Mino-DCs ameliorates clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.