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

Abstract

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-β, 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-β.