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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: CNS Neuroscience & Therapeutics; v. 19, n. 9, p. 682-687, SEP 2013.
• Web of Science Citations: 12

Abstract

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)

• FAPESP's process: 12/04565-0 - Immunoregulatory function of HLA-G molecules in multiple sclerosis and experimental autoimmune encephalomyelitis
• Grantee: Leonilda Maria Barbosa dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/18728-5 - Study of migratory, effector and regulatory pattern of autoreactive t lymphocytes, previously transduced with GFP in experimental demyelinating diseases
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 11/15175-5 - Analysis of the effect of G-CSF in the neuritogenic cells migration and effector pattern during the clinical course of experimental autoimmune neuritis induced in Lewis rats
• Grantee: Fernando Pradella
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/15639-1 - Effect of type I interferon in the induction of tolerogenic function of plasmacytoid dendritic cells in experimental autoimmune encephalomyelitis
• Grantee: Mariana Peres Almeida Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/09879-2 - Study of the role of the immunoregulatory molecule HLA-G in Multiple sclerosis and Experimental autoimmune encephalomyelitis
• Grantee: Adriel dos Santos Moraes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/01408-0 - Study of migratory, effector and regulatory pattern of autoreactive T lymphocytes, previously transduced with GFP in experimental demyelinating diseases
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Scholarships in Brazil - Young Researchers