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| Author(s): |
Marcos Henrique Rosa
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2020-03-05 |
| Examining board members: |
José Carlos Farias Alves Filho;
Paulo Louzada Júnior;
João Paulo de Biaso Viola
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| Advisor: | José Carlos Farias Alves Filho |
| Abstract | |
FoxP3 + regulatory T cells (Tregs) play crucial suppressive functions for homeostasis of immune system. It has been widely demonstrated that the cellular metabolism contributes effectively to the proliferation, differentiation and function of the cells of immune system, being the glycolytic pathway an important point of integration of different metabolic pathways. In light of this, the enzyme phosphofructokinase-1 (PFK- 1), which catalyzes the conversion of fructose 6-phosphate to fructose 1,6- bisphosphate, acts in a limiting step of glycolytic flow. The activity of PFK-1 is regulated allosterically by the metabolite fructose-2,6-biphosphate (F2,6BP), which is a product of the enzyme 6-phosphofructo-2-kinase / fructose-2,6-bisphosphatase 3 (PFKFB3). It is well known that inhibition of the kinase activity of PFKFB3 may accumulate substrates for other important pathways of cellular metabolism. Although oxidative metabolism has been reported to play an important role in the development and function of Tregs, preliminary results from our laboratory have demonstrated that de hexosamines pathway is important to stability and differentiation of Treg and inhibition of the enzyme PFKFB3 promotes a greater differentiation of Tregs. Therefore, the present work aimed to understand the role of the enzyme PFKFB3 in the differentiation and function of Tregs, and verified an improvement of the clinical signs in mice treated with enzyme inhibitor PFKFB3 that proved to be a possible target for the development of therapy for inflammatory diseases. (AU) | |
| FAPESP's process: | 18/23910-6 - Role of PFKFB-3 enzyme in regulatory t cells |
| Grantee: | Marcos Henrique Rosa |
| Support Opportunities: | Scholarships in Brazil - Master |