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Determination of the epigenetic signature related to human neutrophil polarization to N1 and N2 profiles

Grant number: 18/12641-4
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2018
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fabiani Gai Frantz
Grantee:Cícero José Luíz dos Ramos Almeida
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Epigenetic changes are by definition inheritable changes of the functional genome that do not alter the DNA nucleotide sequence. Cell differentiation is one of the events under epigenetic control, macrophages and T cells undergo changes such as methylation / acetylation to differentiate into M1, M2, Th1, Th2, Th17, for example. The cellular plasticity of cells of the innate and adaptive immune system may then be under epigenetic control, when the infectious or inflammatory microenvironment defines the cell differentiation or polarization profile. In the tumor environment, polarized neutrophils were identified for the N1 and N2 profiles, respectively associated with control and tumor susceptibility. Neutrophils have also been assigned controversial roles in tuberculosis. Previous results from our research group showed that patients with active tuberculosis might present neutrophils polarized in the circulating blood, which correlated with the severity of the disease. Also, in vitro, we have demonstrated that neutrophils can acquire the polarized phenotype for N1 or N2 according to the cytokines present in the culture. One of the interests of our research group is to study mechanisms and functions of innate immune system cells that may be related to epigenetic control. Thus, in this project, our objective will be to investigate which epigenetic alterations are under control of the in vitro polarization of neutrophils, as it has been demonstrated for other cells of the immune system that undergo plasticity according to the microenvironment.