[Frontiers in Bioscience S3, 1007-1020, June 1, 2011]

New role of glutamate as an immunoregulator via glutamate receptors and transporters

Hongyu Xue1, Catherine J. Field2

1Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, 2Department of Agriculture, Food and Nutritional Science, University of Alberta, 4-126A HRIF East, Edmonton, AB, T6G 2E1, Canada

TABLE OF CONTENTS

1. Abstract
2. Introduction - Role of glutamate (Glu) in immune function
3. Regulatory role of glutamatergic system expressed on immune cells
3.1. GluTs on immune cells - a mechanistic focus on regulation of Glutathione (GSH) synthesis
3.2. GluR expression on immune cells
3.2.1. mGluRs expression in immune cells
3.2.1.1. Thymocytes
3.2.1.2. T lymphocytes
3.2.1.3. Dendritic cells
3.2.2. iGluR expression in immune cells
3.2.2.1. PBMC
3.2.2.2. Lymphocytes
3.3. The regulator role of Glu in T cell activation/proliferation occurs via GluRs
3.3.1. A potential link between high intestinal Glu content and oral tolerance development?
4. Conclusions
5. Acknowledgements
6. References

1. ABSTRACT

Accumulating evidence suggests that the amino acid glutamate (Glu) may play a role in mediating immune function. The demonstration of Glu receptors (GluR) and Glu transporters (GluT) on a variety of immune cells suggests that Glu has a functional role in immunoregulation well beyond its role as a neurotransmitter. The extracellular Glu concentration plays a key role in the regulation of GSH synthesis in immune cells via 2 key GluTs (i.e., Xc- and X-AG systems). Emerging evidence also suggests a role of Glu as signaling molecule in immune cells via ionotropic GluRs (iGluRs) and metabotropic GluRs (mGluRs). In vitro, extracellular Glu concentration has been shown to exert a dose-dependent regulation on lymphocyte activation/proliferation. Specifically, Given the exceedingly high intestinal Glu concentration, these finding are suggestive of a potential role for Glu in modulating immune function and promoting tolerance in the gut associated lymphoid tissues.