Carbosilane Dendrimer 2G-NN16 Represses Tc17 Differentiation in Primary T CD8+ Lymphocytes

• Published in: Molecular pharmaceutics Vol. 9; no. 1; pp. 102 - 110
• Main Authors: Gras, Rafael, García, María I, Gómez, Rafael, de la Mata, F. Javier, Muñoz-Fernández, M. Angeles, López-Fernández, Luís A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.2012
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - drug effects; Cell Survival - drug effects; Cells, Cultured; Dendrimers - adverse effects; Dendrimers - chemistry; Dendrimers - pharmacology; Down-Regulation - drug effects; Gene Expression Profiling; Gene Transfer Techniques - adverse effects; Humans; Interleukin-17 - genetics; Interleukin-17 - metabolism; Nanoparticles - adverse effects; Nanoparticles - chemistry; Oligonucleotide Array Sequence Analysis; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA, Messenger - metabolism; Silanes - adverse effects; Silanes - chemistry; Silanes - pharmacology; Up-Regulation - drug effects; Tc17 cells; nanoparticles; dendrimers; immune response; gene expression
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp200305u

We studied changes in gene expression induced by the carbosilane dendrimer 2G-NN16 to evaluate their potential as a vehicle for gene therapy and as medication. Global gene expression profiles on CD8+ T lymphocytes reveal that ribosomal proteins are induced in the presence of 2G-NN16. IL17A and IL17F, the principal interleukins secreted by Tc17 cells, a subset of CD8+ T lymphocytes, were down-regulated when cultured in the presence of this dendrimer. Microarray results were confirmed by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 2G-NN16 also showed a high potential for in vitro inhibition of Tc17 differentiation of CD8+ T lymphocytes in the presence of the Tc17 differentiation molecules IL6 and TGF-B1. These findings suggest that 2G-NN16 could facilitate drug delivery and may be used to treat inflammatory processes driven by Tc17 cells.