Evaluation of sodium chloride effect on dendritic cells maturation during efferocytosis

• Grant number: 16/07972-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2016
• Effective date (End): July 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Letícia de Aquino Penteado
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 11/17611-7 - Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2, AP.JP

Abstract

Efferocytosis by dendritic cells (DC) is one of the main sources for self-antigen presentation, which leads to generation of tolerogenic DC (tDC), characterized by low expression of MHC-II, CD86 and CCR7 molecules, and production of anti-inflammatory mediators, such as TGF-², IL-10 and PGE2, thus promoting T reg cells differentiation. Recently, studies have shown that excessive salt intake has a pivotal role in creating a pro-inflammatory microenvironment, for example, enhancement of M1 macrophages activation, inhibition of M2 macrophages differentiation and a significant increase in Th17 pathogenic cells in EAE model. However, until now, nothing has been described about the effect of high NaCl concentrations in DC activation and maintenance of peripheral tolerance. Therefore, the hypothesis of our study is that efferocytosis by DC in a microenvironment affected by high concentrations of NaCl, would lead to the activation of these DC and production of soluble mediators that promotes activation and differentiation of autoreactive Th17 cells, breaking tolerance to self antigens.