The Non-canonical Role of Metabolic Enzymes in Immune Cells and Its Impact on Diseases

Abstract

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. 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. 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.