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PGE2 immunomodulatory role in Th17 differentiation during the phagocytosis of infected apoptotic cells event

Grant number: 11/20199-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2012
Effective date (End): July 31, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Alexandra Ivo de Medeiros
Grantee:Felipe Fortino Verdan da Silva
Home 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
Associated scholarship(s):13/27028-2 - Stability and plasticity of Th9 cells: role of PU.1, BE.EP.DR

Abstract

The phagocytosis of apoptotic cells, also called efferocytosis, is a dynamic process critical for tissue homeostasis after injury. We and other groups previously shown that phagocytosis of apoptotic cells promotes the synthesis of anti-inflammatory mediators such as PGE2, TGF-² and IL-10 that may result in the suppression of host defense against microorganisms. However, an elegant study using infected apoptotic cells showed that phagocytosis of these cells promotes the generation of anti-inflammatory cytokines such as TGF-² but also IL-6 and IL-23, resulting an immunostimulatory effect, the differentiation of Th17 cells. The role of PGE2 in adaptive immunity has been investigated as lymphocyte differentiation and activation of Th1, Th17 and Treg. Our preliminary results show that phagocytosis of infected apoptotic cells, and inflammatory cytokines also induces the production of high levels of PGE2. However, of the involvement of this lipid mediator in the context of phagocytosis of infected apoptotic cells and the mechanism by which PGE2 can work synergistically with TGF-², IL-6 and IL-23 in the process of Th17 cell differentiation is unknown. The hypothesis of this project is: to study the role of PGE2 from the efferocytosis of infected apoptotic cells in the Th17 cell differentiation.