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The Journal of Immunology, 2006, 177: 2765-2769.
Copyright © 2006 by The American Association of Immunologists, Inc.

CUTTING EDGE

Cutting Edge: Critical Role for A2A Adenosine Receptors in the T Cell-Mediated Regulation of Colitis1

Makoto Naganuma, Elizabeth B. Wiznerowicz, Courtney M. Lappas, Joel Linden, Mark T. Worthington and Peter B. Ernst2

Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908

A2A adenosine receptors (A2AAR) inhibit inflammation, although the mechanisms through which adenosine exerts its effects remain unclear. Although the transfer of regulatory Th cells blocks colitis induced by pathogenic CD45RBhigh Th cells, we show that CD45RBlow or CD25+ Th cells from A2AAR-deficient mice do not prevent disease. Moreover, CD45RBhigh Th cells from A2AAR-deficient mice were not suppressed by control CD45RBlow Th cells. A2AAR agonists suppressed the production of proinflammatory cytokines by CD45RBhigh and CD45RBlow T cells in association with a loss of mRNA stability. In contrast, anti-inflammatory cytokines, including IL-10 and TGF-beta, were minimally affected. Oral administration of the A2AAR agonist ATL313 attenuated disease in mice receiving CD45RBhigh Th cells. These data suggest that A2AAR play a novel role in the control of T cell-mediated colitis by suppressing the expression of proinflammatory cytokines while sparing anti-inflammatory activity mediated by IL-10 and TGF-beta.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by the Crohn’s and Colitis Foundation of America (CCFA), National Institutes of Health Grants DK50980, AI069880, and RR00175 (to P.B.E.), and the Immunology and Cell Isolation Core as well as the Morphology/Imaging Core of the University of Virginia (Charlottesville, VA) Digestive Health Research Center (DK67629). M.N. is supported by a fellowship from the CCFA.

2 Address correspondence and reprint requests to Dr. Peter B. Ernst, Department of Internal Medicine, University of Virginia, P.O. Box 800708, Charlottesville, VA, 22908-0708. E-mail address: Pernst{at}virginia.edu

3 Abbreviations used in this paper: IBD, inflammatory bowel disease; Treg, regulatory T cell; A2AAR, adenosine 2A adenosine receptor; ARE, adenine- and uracil-rich element.




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