Stumpfova Zuzana, Hezova Renata, Meli Albano Carlo, Slaby Ondrej, Michalek Jaroslav
Department of Pharmacology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
CEITEC, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic ; Masaryk Memorial Cancer Institute, Zlutý Kopec 7, 65653 Brno, Czech Republic.
Mediators Inflamm. 2014;2014:259689. doi: 10.1155/2014/259689. Epub 2014 Apr 1.
Dendritic cells (DCs) belong to the immune system and are particularly studied for their potential to direct either an activated or tolerogenic immune response. The roles of microRNAs (miRNAs) in posttranscriptional gene expression regulation are being increasingly investigated. This study's aim is to evaluate the miRNAs' expression changes in prepared human immature (iDCs), activated (aDCs), and tolerogenic dendritic cells (tDCs). The dendritic cells were prepared using GM-CSF and IL-4 (iDC) and subsequently maturated by adding LPS and IFN-γ (aDC) or IL-10 and TGF-β (tDC). Surface markers, cytokine profiles, and miRNA profiles were evaluated in iDC, tDC, and aDC at 6 h and 24 h of maturation. We identified 4 miRNAs (miR-7, miR-9, miR-155 and miR-182), which were consistently overexpressed in aDC after 6 h and 24 h of maturation and 3 miRNAs (miR-17, miR-133b, and miR-203) and miR-23b cluster solely expressed in tDC. We found 5 miRNAs (miR-10a, miR-203, miR-210, miR-30a, and miR-449b) upregulated and 3 miRNAs downregulated (miR-134, miR-145, and miR-149) in both tDC and aDC. These results indicate that miRNAs are specifically modulated in human DC types. This work may contribute to identifying specific modulating miRNAs for aDC and tDC, which could in the future serve as therapeutic targets in the treatment of cancer and autoimmune diseases.
树突状细胞（DCs）属于免疫系统，因其具有引导激活或诱导免疫耐受反应的潜力而受到特别研究。微小RNA（miRNAs）在转录后基因表达调控中的作用正受到越来越多的研究。本研究的目的是评估在制备的人未成熟树突状细胞（iDCs）、活化树突状细胞（aDCs）和诱导免疫耐受的树突状细胞（tDCs）中miRNAs的表达变化。使用GM-CSF和IL-4制备树突状细胞（iDC），随后通过添加LPS和IFN-γ使其成熟（aDC）或添加IL-10和TGF-β使其成熟（tDC）。在iDC、tDC和aDC成熟6小时和24小时时评估其表面标志物、细胞因子谱和miRNA谱。我们鉴定出4种miRNAs（miR-7、miR-9、miR-155和miR-182），它们在成熟6小时和24小时后的aDC中持续过表达，以及3种miRNAs（miR-17、miR-133b和miR-203）和miR-23b簇仅在tDC中表达。我们发现5种miRNAs（miR-10a、miR-203、miR-210、miR-30a和miR-449b）在tDC和aDC中均上调，3种miRNAs（miR-134、miR-145和miR-149）下调。这些结果表明miRNAs在人DC类型中受到特异性调节。这项工作可能有助于识别aDC和tDC的特异性调节miRNAs，未来它们可作为癌症和自身免疫性疾病治疗的靶点。
