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The role of ectonucleotidase CD39 in the establishment of sepsis-induced immunosuppression

Grant number: 15/25974-3
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): April 30, 2016
Effective date (End): April 29, 2017
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:José Carlos Farias Alves Filho
Grantee:Daniele Carvalho Bernardo Nascimento
Supervisor abroad: Bernhard Ryffel
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Université d'Orléans, France  
Associated to the scholarship:12/10100-0 - The role of ectonucleotidases and adenosine in the establishment of sepsis-induced immunosuppression, BP.PD

Abstract

Immunosuppression has been shown to be one of the major long-term sequels of sepsis survivors, which is mainly characterized by the expansion of regulatory T cells (Tregs). However, the mechanisms underlying this Treg expansion remain poor understood. There are evidences showing that extracellular adenosine can induce Tregs differentiation thought activation of adenosine receptor A2a (A2aR). Interestingly, results obtained during the development of this current project show that pharmacological blockade or genetic deficiency of A2aR reduce the expansion of Tregs and improve the resistance of sepsis-surviving mice against a secondary infection challenge, suggesting that extracellular adenosine is involved, at least in part, with the development of sepsis-induced immunosuppression. The degradation of extracellular ATP by sequential activities of two ectonucleotidases, CD39 and CD73, has been considered as the main pathway for extracellular adenosine production, implicating these enzymes as potential components of sepsis-induced immunosuppression. In order to give continuity to our project, we have set up a collaborative study with Prof. Bernhard Ryffel from CNRS in France to investigate the role of CD39 in the development of sepsis-induced immunosuppression. Therefore, we are applying for BEPE fellowship program to spend 1 year in the laboratory of Prof. Ryffel to develop this project. (AU)