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Whiteside TL, Jackson EK. Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease. Front Immunol. 2013;4:212doi: 10.3389/fimmu.2013.00212.
Whiteside, T. L., & Jackson, E. K. (2013). Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease. Frontiers in immunology, 4212. https://doi.org/10.3389/fimmu.2013.00212
Whiteside, Theresa L, and Jackson, Edwin K. "Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease." Frontiers in immunology vol. 4 (2013): 212. doi: https://doi.org/10.3389/fimmu.2013.00212
Whiteside TL, Jackson EK. Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease. Front Immunol. 2013 Jul 25;4:212. doi: 10.3389/fimmu.2013.00212. eCollection 2013. PMID: 23898333; PMCID: PMC3722515.
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Front Immunol. 2013 Jul 25;4:212. doi: 10.3389/fimmu.2013.00212. eCollection 2013.

Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease.

Frontiers in immunology

Theresa L Whiteside, Edwin K Jackson

Affiliations

  1. Department of Pathology, University of Pittsburgh Cancer Institute , Pittsburgh, PA , USA.

PMID: 23898333 PMCID: PMC3722515 DOI: 10.3389/fimmu.2013.00212

Abstract

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

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