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Am J Clin Exp Immunol 2013;2(1):30-54
Review Article
Changing the energy of an immune response
Meghan M Delmastro-Greenwood, Jon D Piganelli
Diabetes Institute, Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children’s Hospital
of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Immunology, University of
Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
Received November 13, 2012; Accepted January 17, 2013; Epub February 27, 2013; Published March 9, 2013
Abstract: The breakdown of nutrients into the critical energy source ATP is the general purpose of cellular metabolism
and is essential for sustaining life. Similarly, the immune system is composed of different cell subsets that are
indispensable for defending the host against pathogens and disease. The interplay between metabolic pathways and
immune cells leads to a plethora of different signaling pathways as well as cellular activities. The activation of T cells via
glycolysis-mediated upregulation of surface markers, for example, is necessary for an appropriate effector response
against an infection. However, tight regulation of immune cell metabolism is required for protecting the host and
resuming homeostasis. An imbalance of immunological metabolic function and/or metabolic byproducts (reactive
oxygen species) can oftentimes lead to diseases. In the case of cancer, overactive glucose metabolism can lead to
hyperproliferation of cells and subsequent decreases in cytotoxic T cell activity, which attack and destroy the tumor. For
this reason and many more, targeting metabolism in immune cells may be a novel therapeutic strategy for treatment of
disease. The metabolic pathways of immune cells and the possibilities of immunometabolic therapies will be
discussed. (AJCEI1211002).
Keywords: Metabolism, immune response, aerobic glycolysis, oxidative phosphorylation
Address correspondence to: Dr. Jon D Piganelli, Diabetes Institute, Division of Immunogenetics, Department of
Pediatrics, Rangos Research Center, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA
15224, USA. E-mail: jdp51@pitt.edu
Review Article
Changing the energy of an immune response
Meghan M Delmastro-Greenwood, Jon D Piganelli
Diabetes Institute, Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children’s Hospital
of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA; Department of Immunology, University of
Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
Received November 13, 2012; Accepted January 17, 2013; Epub February 27, 2013; Published March 9, 2013
Abstract: The breakdown of nutrients into the critical energy source ATP is the general purpose of cellular metabolism
and is essential for sustaining life. Similarly, the immune system is composed of different cell subsets that are
indispensable for defending the host against pathogens and disease. The interplay between metabolic pathways and
immune cells leads to a plethora of different signaling pathways as well as cellular activities. The activation of T cells via
glycolysis-mediated upregulation of surface markers, for example, is necessary for an appropriate effector response
against an infection. However, tight regulation of immune cell metabolism is required for protecting the host and
resuming homeostasis. An imbalance of immunological metabolic function and/or metabolic byproducts (reactive
oxygen species) can oftentimes lead to diseases. In the case of cancer, overactive glucose metabolism can lead to
hyperproliferation of cells and subsequent decreases in cytotoxic T cell activity, which attack and destroy the tumor. For
this reason and many more, targeting metabolism in immune cells may be a novel therapeutic strategy for treatment of
disease. The metabolic pathways of immune cells and the possibilities of immunometabolic therapies will be
discussed. (AJCEI1211002).
Keywords: Metabolism, immune response, aerobic glycolysis, oxidative phosphorylation
Address correspondence to: Dr. Jon D Piganelli, Diabetes Institute, Division of Immunogenetics, Department of
Pediatrics, Rangos Research Center, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA
15224, USA. E-mail: jdp51@pitt.edu
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