Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
CNS Neurosci Ther. 2013 Sep;19(9):682-7. doi: 10.1111/cns.12121. Epub 2013 Jun 3.
Both Th1 and Th17 cells specific for neuroantigen are described as encephalitogenic in the experimental autoimmune encephalomyelitis (EAE) model.
The proposal of this study was to investigate how carbon nanotubes internalized by antigen-presenting cells (APCs) affect the development of encephalitogenic CD4(+) T cells.
Therefore, we stimulated encephalitogenic T cells in the presence or not of multiwalled carbon nanotube (MWCNT). After the incubation, we analyzed the expression profile of the encephalitogenic T cells and their capacity to induce EAE.
Encephalitogenic CD4(+) T cells cultured with APCs that were previously incubated with MWCNTs do not express IL-17. The adoptive transfer of these cells causes less severe EAE than the transfer of both Th1 and Th17 cells that are not incubated with MWCNTs. These results suggest that the increased IL-27 level produced by the APCs incubated with the carbon nanotubes inhibits the development of Th17 cells. This observation is confirmed by the concomitant reduction in the level of RORγt, which is a transcription factor essential for the development of Th17 cells. Moreover, the incubation of encephalitogenic T cells devoid of Th17 cells with neutralizing anti-IL-27 antibodies restored the production of IL-17.
This finding confirms the suppressive effect of IL-27 on encephalitogenic Th17 cells. The results presented suggest that the stimulation of APCs with carbon nanoparticles prior to neuroantigen presentation affects the development of the Th17 subset of encephalitogenic CD4(+) T lymphocytes and results in less severe EAE.
在实验性自身免疫性脑脊髓炎(EAE)模型中,针对神经抗原的 Th1 和 Th17 细胞都被描述为致脑炎的。
本研究旨在探讨抗原呈递细胞(APC)内吞的碳纳米管如何影响致脑炎性 CD4+T 细胞的发育。
因此,我们在存在或不存在多壁碳纳米管(MWCNT)的情况下刺激致脑炎性 T 细胞。孵育后,我们分析了致脑炎性 T 细胞的表达谱及其诱导 EAE 的能力。
与未用 MWCNT 孵育的 APC 共培养的致脑炎性 CD4+T 细胞不表达 IL-17。与未用 MWCNT 孵育的 Th1 和 Th17 细胞相比,这些细胞的过继转移引起的 EAE 较轻。这些结果表明,与碳纳米管孵育的 APC 产生的 IL-27 水平增加抑制了 Th17 细胞的发育。这一观察结果通过 RORγt 水平的同时降低得到证实,RORγt 是 Th17 细胞发育所必需的转录因子。此外,用中和抗 IL-27 抗体处理缺乏 Th17 细胞的致脑炎性 T 细胞恢复了 IL-17 的产生。
这一发现证实了 IL-27 对致脑炎性 Th17 细胞的抑制作用。这些结果表明,在神经抗原呈递之前用碳纳米颗粒刺激 APC 会影响致脑炎性 CD4+T 淋巴细胞中 Th17 亚群的发育,并导致 EAE 较轻。