The Non-canonical Role of Metabolic Enzymes in Immune Cells and Its Impact on Diseases
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IMMUNOMETABOLISM (NOS CÂMARA, SECTION EDITOR)
The Non-canonical Role of Metabolic Enzymes in Immune Cells and Its Impact on Diseases Renan Willian Alves 1 & Lorena Doretto-Silva 1 & Eloisa Martins da Silva 2 & Cristina Ribas Fürstenau 3 & Vinicius Andrade-Oliveira 4 Accepted: 14 October 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose of Review This review aims to elucidate the new functions of metabolic enzymes and how they impact and modulate the activation and differentiation of immune cells. Macrophages and T cells are components of the innate and adaptive immune systems and play an important role in several diseases. To perform their function, these cells undergo activation and differentiation. It is appreciated that immune cells concurrently reprogram their metabolism of glucose, amino acid, and fatty acid to generate energy and substances essential to perform their function. Recent Findings It was recently described that some metabolism-involved enzymes have unconventional functions upon immune cells. For instance, hexokinase can act as a sensor for bacterial antigens and, in some cases, activate inflammasome assembly. On the other hand, GAPDH and PKM2 regulate the expression of some cytokines, whereas LDH-A blocks the inflammatory response and stearoyl-CoA desaturase promotes the survival of the immune cells. Summary Here, we summarize the recent findings of the non-canonical role of metabolism-related enzymes, mainly in glycolysis, since the influence of these little-known functions in immune cells and immune-mediated diseases is still a focus of recent works. Understanding and appreciating these enzymes and their mechanisms of action may assist in the development of new therapeutic strategies for autoimmunity, cancer, and transplantation. Keywords Hexokinase . Glyceraldehyde-3-phosphate dehydrogenase . α-Enolase . Pyruvate kinase . Lactate dehydrogenase . Stearoyl-CoA desaturases . Immunity
Introduction
Renan Willian Alves and Lorena Doretto-Silva contributed equally to this work. This article is part of the Topical Collection on Immunometabolism * Vinicius Andrade-Oliveira [email protected]; [email protected] 1
Bernardo’s Lab, Center for Human and Natural Sciences, Federal University of ABC (UFABC), Building A, Room 503-3, Av. dos Estados, 5001, Bangú, Santo André, SP, Brazil
2
Laboratory of Clinical and Experimental Immunology, Department of Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
3
Laboratory of Vascular Biochemistry, Center for Human and Natural Science, Federal University of ABC (UFABC), Santo André, Brazil
4
Bernardo’s Lab, Center for Human and Natural Sciences, Federal University of ABC (UFABC), Building B, Room 1035, Av. dos Estados, 5001, Bangú, Santo André, SP 09210-580, Brazil
Immune cells, such as macrophages and T cells, are components of our immune system responsible for maintaining host homeostasis. To perform their function, these quiescent cells first need to be activated and differentiated. As such, T cells must
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