Tolerogenic efficacy of the association MOG/vitamin D analog or MOG/rapamycin on experimental autoimmune encephalomyelitis

• Grant number: 13/26257-8
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2014 - April 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandrina Sartori
• Grantee: Alexandrina Sartori
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Multiple sclerosis (MS) is a progressive inflammatory disease that damages the central nervous system (CNS). The currently available therapies for MS are primarily focused in minimizing the progression of disability and reducing the number of relapses, therefore new prophylactic and therapeutic strategies for MS are necessary. In this context, the present study was designed to determine if a vitamin D analog or rapamycin could be used as tolerogenic adjuvants on experimental autoimmune encephalomyelitis (EAE) development. Initially, the possible toxicity of these two drugs will be tested by determination of body weight, leukogram, calcium and phosphorus seric concentrations and histopathological analysis of kidney and liver. To evaluate the tolerogenic potential of these two drugs, female C57BL/6 mice will be epicutaneously immunized with MOG (myelin oligodendrocyte glycoprotein) in their presence. The most efficient tolerogenic strategy will be then tested considering its therapeutic potential on EAE development. In chronic EAE stage, mice will be euthanized and immune response (cytokine and antibody production) and inflammatory infiltrates in the CNS will be assessed. Lastly, the immunological mechanisms involved in tolerance induction will be evaluated through dendritic and regulatory T (Treg) cells phenotype characterization in lymphoid organs and in the CNS. Besides, cytokine profile will be characterized in the CNS. Our hypothesis is that immunization with a SNC antigen delivered by an epicutaneous route in the presence of these two drugs will induce specific tolerance. Tolerogenic dendritic cells and/or Treg cells are expected to be associated with tolerance elicitation. We suppose that this tolerance will be able to protect mice from EAE development. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MIMURA, LUIZA AYUMI NISHIYAMA; FRAGA-SILVA, THAIS FERNANDA DE CAMPOS; OLIVEIRA, LARISSA RAGOZZO CARDOSO DE; ISHIKAWA, LARISSA LUMI WATANABE; BORIM, PATRICIA APARECIDA; MACHADO, CARLA DE MORAES; JUNIOR, JOSE DE ANCHIETA DE CASTRO E HORTA; FONSECA, DENISE MORAIS DA; SARTORI, ALEXANDRINA. Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 4, FEB 2021. (15/06706-8, 13/26257-8)

GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; NISHIYAMA MIMURA, LUIZA AYUMI; DENADAI, MARINA BONIFACIO; FERNANDES DE SOUZA, WILLIAM DANILO; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; SARTORI, ALEXANDRINA. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?. NEURAL REGENERATION RESEARCH, v. 17, n. 9, p. 10-pg., 2022-09-01. (13/26257-8, 13/01604-7, 19/15980-7, 15/06706-8, 13/14353-2)

CARDOSO DE OLIVEIRA, LARISSA RAGOZO; NISHIYAMA MIMURA, LUIZA AYUMI; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; WATANABE ISHIKAWA, LARISSA LUMI; HENRIQUE FERNANDES, ANA ANGELICA; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; SARTORI, ALEXANDRINA. Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation. FRONTIERS IN PHARMACOLOGY, v. 11, MAR 12 2020. (13/26257-8)

MISSIO, ALINE PARISOTO; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; WATANABE ISHIKAWA, LARISSA LUMI; NISHIYAMA MIMURA, LUIZA AYUMI; DONEGA FRANCA, THAIS GRAZIELA; CARDOSO DE OLIVEIRA, LARISSA RAGOZO; SARTORI, ALEXANDRINA; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA. C57BL/6 and DBA/1 Mice Differ in Their Response to Supplementation with 1,25D and Paricalcitol. BIOMEDICAL AND ENVIRONMENTAL SCIENCES, v. 31, n. 8, p. 613-618, AUG 2018. (13/26257-8)

GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; NISHIYAMA MIMURA, LUIZA AYUMI; CAMPOS FRAGA-SILVA, THAIS FERNANDA; WATANABE ISHIKAWA, LARISSA LUMI; DONEGA FRANCA, THAIS GRAZIELA; SARTORI, ALEXANDRINA. Experimental Autoimmune Encephalomyelitis Is Successfully Controlled by Epicutaneous Administration of MOG Plus Vitamin D Analog. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 16 2017. (13/26257-8, 13/01604-7)