PKM2 contribution to neutrophils' activation in experimental systemic lupus erythematosus onset

• Grant number: 17/01714-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2017
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: José Carlos Farias Alves Filho
• Grantee: Juliana Escher Toller
• 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
• Associated scholarship(s): 19/25298-9 - Role of PKM2 in neutrophil metabolism and function, BE.EP.PD

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the presence of immune complexes and injury to organs and tissues. Although the etiology of SLE remains unknown, neutrophils have been implicated as central actors in the SLE onset, regulating innate and adaptive immunity. Considering recent evidence that the execution of leukocyte functions is closely linked to a change in their metabolic state, it is plausible to hypothesize that changes in neutrophil metabolism may determine a state of activation that contributes to the autoimmunity onset in SLE. Pyruvate kinase (PK) is an enzyme that regulates the final step of glycolysis, producing pyruvate and ATP from its phosphoenolpyruvate (PEP) substrate. Recent studies have demonstrated that pyruvate kinase isozyme type M2 (PKM2), an alternative splice of PK, can undergo post-translational modifications and translocate to the nucleus, acting as a transcriptional cofactor of STAT3 and HIF1± and, consequently, modulating the expression of inflammatory genes. However, the role of PKM2 in the regulation of neutrophils' glycolytic metabolism and in the pathogenesis of SLE is not established. Thus, this work aims to investigate whether changes in PKM2 expression and/or function contribute to neutrophil activation and experimental SLE onset. (AU)

Scientific publications

(4)

(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)

LUIZ, JOAO PAULO M.; TOLLER-KAWAHISA, JULIANA E.; VIACAVA, PAULA R.; NASCIMENTO, DANIELE C.; PEREIRA, PRISCILLA T.; SARAIVA, ANDRE L.; PRADO, DOUGLAS S.; LEBERT, MARC; GIURISATO, EMANUELE; TOURNIER, CATHY; et al. MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of Leukocyte Biology, AUG 2020. (17/20692-5, 13/08216-2, 11/12671-1, 17/01714-8, 16/05377-3)

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)

TOLLER-KAWAHISA, JULIANA ESCHER; HIROKI, CARLOS HIROJI; SILVA, CAMILA MEIRELLES DE SOUZA; NASCIMENTO, DANIELE CARVALHO; PUBLIO, GABRIEL AZEVEDO; MARTINS, TIMNA VARELA; DAMASCENO, LUIS EDUARDO ALVES; VERAS, FLAVIO PROTASIO; VIACAVA, PAULA RAMOS; SUKESADA, FABIO YUJI; et al. The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils. NATURE COMMUNICATIONS, v. 14, n. 1, p. 16-pg., 2023-07-17. (13/08216-2, 19/25298-9, 17/01714-8, 20/02207-5)

LUIZ, JOAO PAULO M.; TOLLER-KAWAHISA, JULIANA E.; VIACAVA, PAULA R.; NASCIMENTO, DANIELE C.; PEREIRA, PRISCILLA T.; SARAIVA, ANDRE L.; PRADO, DOUGLAS S.; LE BERT, MARC; GIURISATO, EMANUELE; TOURNIER, CATHY; et al. MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of Leukocyte Biology, v. 108, n. 4, p. 9-pg., 2020-08-03. (16/05377-3, 17/20692-5, 17/01714-8, 13/08216-2, 11/12671-1)