Glucose and glycated albumin effect over monocyte-induced dendritic cell (mo-DC) from heathy donors and type 1 diabetic patients.

• Grant number: 14/26437-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2015
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Thiago Andrade Patente
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/00719-9 - Effect of hyperglycaemia and glucose concentration on tolerogenic properties of dendritic cells: clues for diabetes associated inflammation, BE.EP.DR

Abstract

Type 1 diabetes mellitus (T1DM) is a complex autoimmune disease, where dendritic cells (DCs) play a relevant role. DCs are a subtype of cells specialized in antigen capture, processing and presentation, thus triggering the response of T lymphocytes. Performing these functions, DCs may generate immunity or tolerance, depending on the extracellular signals they receive. DCs that receive tolerogenic signals are characterized by their ability to generate, in vitro, CD4+CD25+FoxP3+ T lymphocytes and to induce an anergic state in CD4+ effector T lymphocytes. Recently, many efforts have been made to use (potentially) tolerogenic DCs as a tool for the treatment of autoimmune diseases, such as T1DM or in the context of organ transplantation. However, a major concern with respect to the infusion of tolerogenic DCs in humans is their functional plasticity. DCs are very sensitive to environmental signals and, when exposed to a patients' microenvironment, may change their functional phenotype, so that tolerogenic DCs may, instead, stimulate the immune response. Therefore, this study aims to evaluate the effects of high glucose levels and advanced glycation end products (AGEs), two stimuli present in poorly controlled type 1 diabetes patients, on tolerogenic DCs. These DCs will be generated ex vivo from monocytes of TIDM patients or of healthy donors, and will have their membrane phenotype, their transcriptional profile and their ability to activate different subpopulations of T lymphocytes evaluated and compared.

Scientific publications

(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)

ANDRADE PATENTE, T.; ARRUDA DE OLIVEIRA, A.; PEREIRA PINHO, M.; CRUZ BERGAMI-SANTOS, P.; CARDILLO CORREA-GIANELLA, M. L.; MARZAGAO BARBUTO, J. A.. Monocyte-Derived Dendritic Cells generated in the presence of 1,25(OH)2D3 are modulated by Glucose Concentration. European Journal of Immunology, v. 48, p. 2-pg., 2018-05-01. (14/26437-9)

PATENTE, THIAGO A.; PINHO, MARIANA P.; OLIVEIRA, ALINE A.; EVANGELISTA, GABRIELA C. M.; BERGAMI-SANTOS, PATRICIA C.; BARBUTO, JOSE A. M.. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. FRONTIERS IN IMMUNOLOGY, v. 9, JAN 21 2019. (14/25988-1, 16/01137-8, 14/26437-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PATENTE, Thiago Andrade. Metabolic Regulatory Pathways in Tolerogenic Bias Dendritic Cells. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.