REVIEW ARTICLE
Front. Immunol., 25 July 2013 | doi: 10.3389/fimmu.2013.00212
Adenosine and prostaglandin E2 production by human inducible regulatory T cells in health and disease
- 1Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
- 2Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Regulatory T cells (Treg) play a key role in maintaining the balance of immune responses in human health and in disease. Treg come in many flavors and can utilize a variety of mechanisms to modulate immune responses. In cancer, inducible (i) or adaptive Treg expand, accumulate in tissues and peripheral blood of patients, and represent a functionally prominent component of CD4+ T lymphocytes. Phenotypically and functionally, iTreg are distinct from natural (n) Treg. A subset of iTreg expressing ectonucleotidases CD39 and CD73 is able to hydrolyze ATP to 5′-AMP and adenosine (ADO) and thus mediate suppression of those immune cells which express ADO receptors. iTreg can also produce prostaglandin E2 (PGE2). The mechanisms responsible for iTreg-mediated suppression involve binding of ADO and PGE2 produced by iTreg to their respective receptors expressed on T effector cells (Teff), leading to the up-regulation of adenylate cyclase and cAMP activities in Teff and to their functional inhibition. The potential for regulating these mechanisms by the use of pharmacologic inhibitors to relieve iTreg-mediated suppression in cancer suggests the development of therapeutic strategies targeting the ADO and PGE2 pathways.
Keywords: cancer inducible regulatory T cells, natural regulatory T cells, tumor microenvironment
Citation: Whiteside TL and Jackson EK (2013) Adenosine and prostaglandin E2 production by human inducible regulatory T cells in health and disease. Front. Immunol. 4:212. doi: 10.3389/fimmu.2013.00212
Received: 15 May 2013; Paper pending published: 25 May 2013;
Accepted: 11 July 2013; Published online: 25 July 2013.
Accepted: 11 July 2013; Published online: 25 July 2013.
Edited by:
Eyad Elkord, United Arab Emirates University, UAE; University of Salford and University of Manchester, UK
Reviewed by:
Masahide Tone, Cedars-Sinai Medical Center, USALionel Apetoh, Institut National de la Santé et de la Recherche Médicale, France
Copyright: © 2013 Whiteside and Jackson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Theresa L. Whiteside, Department of Pathology, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA e-mail: whitesidetl@upmc.edu
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