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Role of nitric oxide (NO) in the modulation of experimental autoimmune encephalomyelitis (EAE) after the adoptive transfer of tolerogenic dendritic cells: influence of the MyD88-mTOR-iNOS and STAT1/3-iNOS axis

Grant number: 14/02631-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2014
Effective date (End): April 30, 2016
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Liana Maria Cardoso Verinaud
Grantee:Rodolfo Thomé
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Dendritic cells (DCs), antigen-presenting cells, are able to polarize the immune response towards an inflammatory or anti-inflammatory context depending on its maturation/activation status, leading to the generation of regulatory T cells or Th1, Th2, Th9 and Th17 profiles. Immature DCs are also called tolerogenic DCs. The modulation of DCs may be an innovative approach to control chronic inflammation, where some drugs, like dexamethasone- that has an immune-modulatory action, are being employed. Recently, our group demonstrated that chloroquine reduces the severity of Experimental Autoimmune Encephalomyelitis (EAE). Since the chronic consumption of chloroquine leads to toxic effects, we demonstrated that chloroquine is able to modulate dendritic cells towards a tolerogenic status, and upon adoptive transfer onto EAE-bearing mice disease severity was reduced by a NO-dependent mechanism. A growing body of evidences indicate that mTOR and STAT1/STAT3 signaling cascades play a role in the modulation of DCs especially in the production of nitric oxide. Therefore, the aim of this study is to evaluate the role of nitric oxide produced by chloroquine/artesunato-treated dendritic cells in the modulation of Experimental Autoimmune Encephalomyelitis. We will investigate the influence of MyD88-mTOR-iNOS and STAT1/3-iNOS axis in the modulatory function of tolerogenic dendritic cells as well. (AU)

Scientific publications (6)
(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)
THOME, RODOLFO; BONFANTI, AMANDA PIRES; RASOULI, JAVAD; MARI, ELISABETH ROSE; ZHANG, GUANG-XIAN; ROSTAMI, ABDOLMOHAMAD; VERINAUD, LIANA. Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic activity. European Journal of Immunology, v. 48, n. 7, p. 1228-1234, JUL 2018. Web of Science Citations: 3.
DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; THOME, RODOLFO; FELISBINO, MARINA BARRETO; BONFANTI, AMANDA PIRES; WATANABE ISHIKAWA, LARISSA LUMI; SARTORI, ALEXANDRINA; BURGER, EVA; VERINAUD, LIANA. Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis. PLoS One, v. 11, n. 10 OCT 13 2016. Web of Science Citations: 1.
THOME, RODOLFO; DE CARVALHO, ANA CAROLINA; DA COSTA, THIAGO ALVES; WATANABE ISHIKAWA, LARISSA LUMI; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; SARTORI, ALEXANDRINA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; VERINAUD, LIANA. Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System. CNS Neuroscience & Therapeutics, v. 22, n. 8, p. 707-714, AUG 2016. Web of Science Citations: 5.
DI GANGI, ROSARIA; DA COSTA, THIAGO ALVES; THOME, RODOLFO; PERON, GABRIELA; BURGER, EVA; VERINAUD, LIANA. Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs. BMC INFECTIOUS DISEASES, v. 16, MAY 17 2016. Web of Science Citations: 2.
DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; MARTINS, PAULA; FIGUEIREDO LONGHINI, ANA LEDA; ZANUCOLI, FABIO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; STACH-MACHADO, DAGMAR RUTH; BURGER, EVA; VERINAUD, LIANA; THOME, RODOLFO. Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8(+) T cells. Immunology, v. 146, n. 3, p. 486-495, NOV 2015. Web of Science Citations: 3.
VERINAUD, LIANA; PINTO LOPES, STEFANIE COSTA; NARANJO PRADO, ISABEL CRISTINA; ZANUCOLI, FABIO; DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; ISSAYAMA, LUIDY KAZUO; CARVALHO, ANA CAROLINA; BONFANTI, AMANDA PIRES; NIEDERAUER, GUILHERME FRANCIO; DURAN, NELSON; MARANHAO COSTA, FABIO TRINDADE; RODRIGUES OLIVEIRA, ALEXANDRE LEITE; DA CRUZ HOEFLING, MARIA ALICE; STACH MACHADO, DAGMAR RUTH; THOME, RODOLFO. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells. PLoS One, v. 10, n. 5 MAY 4 2015. Web of Science Citations: 5.

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