The Suppressive Effect of IL-27 on Encephalitogenic Th17 Cells Induced by Multiwalled Carbon Nanotubes Reduces the Severity of Experimental Autoimmune Encephalomyelitis

Autor(es):Mostrar menos -

Moraes, Adriel S. ^[1] ; Paula, Rosemeire F. O. ^[1] ; Pradella, Fernando ^{[1, 2]} ; Santos, Mariana P. A. ^{[1, 2]} ; Oliveira, Elaine C. ^[1] ; von Glehn, Felipe ^[1] ; Camilo, Daniela S. ^{[3, 1]} ; Ceragioli, Helder ^[3] ; Peterlevitz, Alfredo ^[3] ; Baranauskas, Vitor ^[3] ; Volpini, Walkyria ^[1] ; Farias, Alessandro S. ^{[1, 2]} ; Santos, Leonilda M. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Neuroimmunol Unit, Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Neuroimmunomodulat Grp, Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CNS Neuroscience & Therapeutics; v. 19, n. 9, p. 682-687, SEP 2013.
• Citações Web of Science: 12

Resumo

Background Both Th1 and Th17 cells specific for neuroantigen are described as encephalitogenic in the experimental autoimmune encephalomyelitis (EAE) model. Aim 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. Methods 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. Results 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 RORt, 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. Conclusion 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. (AU)

• Processo FAPESP: 12/04565-0 - Estudo da função imunoreguladora da molécula HLA-G na esclerose múltipla e na encefalomielite experimental auto-imune
• Beneficiário: Leonilda Maria Barbosa dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/18728-5 - Estudo do padrão migratório, efetor e regulador dos Linfócitos T auto-reativos, previamente transduzidos com GFP, nas doenças desmielinizantes experimentais
• Beneficiário: Alessandro dos Santos Farias
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 11/15175-5 - Análise do efeito do G-CSF no padrão migratório e efetor das células neuritogênicas durante a evolução clínica da Neurite Experimental Auto-imune induzida em ratos Lewis
• Beneficiário: Fernando Pradella
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/15639-1 - Efeito do interferon tipo I na função tolerogênica das células dendríticas plasmocitoides na encefalomielite experimental autoimune
• Beneficiário: Mariana Peres Almeida Santos
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/09879-2 - Estudo da função imunoreguladora da molécula HLA-G na Esclerose múltipla e na Encefalomielite experimental auto-imune.
• Beneficiário: Adriel dos Santos Moraes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/01408-0 - Estudo do padrão migratório, efetor e regulador dos linfócitos T auto-reativos, previamente transduzidos com GFP, nas doenças desmielinizantes experimentais
• Beneficiário: Alessandro dos Santos Farias
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores