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

  • Immunometabolism (NOS Câmara, Section Editor)
  • Published:
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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.

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Acknowledgments

We would like to thank our colleagues Dr. Chirag C. Patel and Dr. Im-Hong Sun at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, and Dr. Min-hee Oh at Yale University for reading and editing the manuscript.

Funding

This work is supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grant number: 19/14755-0). V-A.O. is a fellow of the PEW Latin American Program, Pew Charitable Trust.

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  1. Renan Willian Alves and Lorena Doretto-Silva contributed equally to this work.

Authors and Affiliations

  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

    Renan Willian Alves & Lorena Doretto-Silva

  2. Laboratory of Clinical and Experimental Immunology, Department of Medicine, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Eloisa Martins da Silva

  3. Laboratory of Vascular Biochemistry, Center for Human and Natural Science, Federal University of ABC (UFABC), Santo André, Brazil

    Cristina Ribas Fürstenau

  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

    Vinicius Andrade-Oliveira

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Alves, R.W., Doretto-Silva, L., da Silva, E.M. et al. The Non-canonical Role of Metabolic Enzymes in Immune Cells and Its Impact on Diseases. Curr. Tissue Microenviron. Rep. 1, 221–237 (2020). https://doi.org/10.1007/s43152-020-00020-x

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