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

Grant number: 17/01714-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2017
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:José Carlos Farias Alves Filho
Grantee:Juliana Escher Toller Kawahisa
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

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)