Role of PFKFB-3 enzyme in regulatory t cells

• Grant number: 18/23910-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2019
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Marcos Henrique Rosa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

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 6phosphate 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-2,6biphosphate (F2,6BP), which is a product of the enzyme 6-phosphofructo-2kinase/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 inhibition of the enzyme PFKFB3 promotes a greater differentiation of Tregs. Therefore, the present project aims to understand the role of the enzyme PFKFB3 in the differentiation and function of Tregs, which may provide a possible target for the development of therapy for inflammatory diseases. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES DAMASCENO, LUIS EDUARDO; PRADO, DOUGLAS SILVA; VERAS, FLAVIO PROTASIO; FONSECA, MIRIAM M.; TOLLER-KAWAHISA, JULIANA E.; ROSA, MARCOS HENRIQUE; PUBLIO, GABRIEL AZEVEDO; MARTINS, TIMNA VARELA; RAMALHO, FERNANDO S.; WAISMAN, ARI; et al. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. JOURNAL OF EXPERIMENTAL MEDICINE, v. 217, n. 10, OCT 2020. (13/08216-2, 16/05377-3, 17/01714-8, 18/23910-6, 16/10280-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ROSA, Marcos Henrique. Role of enzime 6-phosphofructo-2-kinase / fructose-2,6-biophosphatase 3 (PFKFB-3) in regulatory T cells. 2020. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.