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Involvement of the enzyme pyruvate kinase M2 (PKM2) in the differentiation of Th17 lymphocytes and pathogenesis of experimental autoimmune encephalomyelitis

Grant number: 16/10280-9
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2016
Effective date (End): January 31, 2018
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:José Carlos Farias Alves Filho
Grantee:Luis Eduardo Alves Damasceno
Home 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

Over the past few years, an important highlight has been given to Th17 lymphocytes for the development and maintenance of autoimmunity-associated inflammation. Hence, the identification of cellular targets that modulate the differentiation and function of those cells may provide novel therapeutical approaches for the treatment of autoimmune diseases. In this framework, recent evidences have demonstrated that Th17 lymphocytes undergo metabolic reprogramming during their differentiation. That reprogrammation involves an increase of the aerobic glycolysis, a phenomenon described in tumour cells that is known as Warburg effect. Pyruvate kinase M2 (PKM2) is an enzyme that regulates the final step of glycolysis converting its substrate phosphoenolpyruvate (PEP) into pyruvate and ATP molecules. Interestingly, certain cellular activation stimuli may induce expression, phosphorylation and conformational switch of PKM2, so that might be able to translocate into the nucleus and acting as protein kinase, which phosphorylates transcription factors, such as STAT3, and/or acting as a transcription coactivator of HIF-1±. In this context, it has been demonstrated that STAT3 and HIF-1± play a critical role in the Th17 cells differentiation. Nonetheless, there are no reports regarding the PKM2 role in Th17 differentiation or its involvement in autoimmune diseases. Therefore, the present study proposes to investigate the role of PKM2 in the differentiation of Th17 lymphocytes as well as in the pathogenesis of experimental autoimmune encephalomyelitis (EAE).

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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; CUNHA, FERNANDO QUEIROZ; CUNHA, THIAGO MATTAR; ALVES-FILHO, JOSE CARLOS. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. JOURNAL OF EXPERIMENTAL MEDICINE, v. 217, n. 10 OCT 2020. Web of Science Citations: 0.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DAMASCENO, Luis Eduardo Alves. Involvement of the enzyme Pyruvate Kinase M2 (PKM2) in the differentiation of Th17 lymphocytes and pathogenesis of experimental autoimmune encephalomyelitis. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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