Study of regulatory molecules in multiple sclerosis and experimental autoimmune encephalomyelitis

Author(s)

Adriel dos Santos Moraes

• Document type: Doctoral Thesis
• Institution: Universidade Estadual de Campinas, Instituto de Biologia
• Defense date: 2017
• Advisor: Leonilda Maria Barbosa dos Santos

Abstract

Multiple sclerosis (MS) is a chronic disabling disease of central nervous system (CNS), which affects genetically predisposed persons after a trigger that has yet not to be determined. CD4 T lymphocytes have long been thought to be the most important immune cell subset in the pathogenesis of the disease, mostly because an MS-like disease can be induced in animal models by adoptive transfer of myelin-reactive T cells. In the present study, we demonstrated evidence about the effect of treatment with immunomodulators (IFN-beta and GA) in the activation of regulatory molecules by pDCs of MS patients. The expression of HLA-G and mRNA HLA-G in pDCs, as well as the level of soluble HLA-G in the serum of MS patients was evaluated. Moreover, we were able to demonstrate that pDCs from untreated MS patients do not express IDO when these cells were stimulated by agonist of TLR 9 but the treatment with the immunomodulators restores the expression of IDO to normal values. In terms of expression of cytokines, significant decrease in the expression of TGFß, IL-10, IL-6 and no expression of IL-17 was observed for patients treated with the immunomodulators. Interestingly patients treated with IFN-ß express significantly more IL-27. We also demonstrated that Multi Walled Carbon Nanotubes (MWCNTs), internalized by antigen presenting cells (APCs), stimulates the production of IL-27 by these cells and that this cytokine affects the development of encephalitogenic Th17 cell in Experimental Autoimmune Encephalomyelitis (EAE). EAE, which is a model of multiple sclerosis, is a CD4+ T cell-mediated autoimmune disease that can be induced in susceptible animals either directly through their immunization with constituent proteins of myelin, such as the myelin basic protein (MBP), or passively by the adoptive transfer of sensitized CD4+ T lymphocytes into naïve animals. The expression of cytokines by encephalitogenic T-cell lines was determined, and the results revealed a significant reduction in the expression of IL- 17, which suggests that the development of Th17 cells was impaired. Taken together, our studies help to understand the role of some regulatory molecules in Multiple Sclerosis and EAE development (AU)

• 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 type: Scholarships in Brazil - Doctorate