Influence of the mTOR, STAT1/3 and iNOS signaling pathways in the activity of tolerogenic dendritic cells

• Grant number: 14/19492-3
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2015
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Liana Maria Cardoso Verinaud
• Grantee: Liana Maria Cardoso Verinaud
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Rodolfo Thomé

Abstract

Dendritic cells (DCs) 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. An increasing number of studies have demonstrated that DC modulation is an innovative approach to control chronic inflammation observed in most autoimmune diseases, such as Multiple Sclerosis and Rheumatoid Arthritis. In this context, our group demonstrated that chloroquine (CQ), an antimalarial drug, generated tolerogenic dendritic cells (DC-CQ) in vitro. We also demonstrated that DC-CQ induced the differentiation of regulatory T cells while suppressing the activation of effector T cells. Notwithstanding, adoptive transfer of DC-CQ reduced autoimmune neuro-inflammation in a mouse model of Multiple Sclerosis, the Experimental Autoimmune Encephalomyelitis (EAE). These findings foster the possibility of adjunct administration of tolerogenic dendritic cells in the treatment of autoimmune diseases. However, literature data are scarce regarding the signaling pathways involved in the activity of tolerogenic DCs. In this context, this project aim to investigate the influence of the intracellular signaling cascades involved in the metabolic control (mTOR), cytokine signaling (STAT1/3) and effector function (nitric oxide, NO) over the suppressive activity of tolerogenic dendritic cells. We believe that a better understanding of the mechanisms that govern the tolerogenic function of DCs may provide a spectrum of possibilities and discovery of new compounds able to modulate dendritic cells and thus contribute to the development of new approaches in the treatment of autoimmune diseases. (AU)

Scientific publications

(4)

(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; 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. (14/19492-3, 14/02631-0, 14/11588-1)

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. (14/19492-3, 13/08194-9, 12/03238-5, 12/22131-7, 13/01401-9, 14/02631-0)

THOMAZ, LIVIA DE LIMA; PERON, GABRIELA; OLIVEIRA, JANINE; DA ROSA, LARISSA CAMARGO; THOME, RODOLFO; VERINAUD, LIANA. The impact of metabolic reprogramming on dendritic cell function. International Immunopharmacology, v. 63, p. 84-93, OCT 2018. (14/19492-3)

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. (14/19492-3, 14/02631-0)