Cutting edge: Critical role for A adenosine receptors in the T cell-mediated regulation of colitis

A adenosine receptors (AAR) inhibit inflammation, although the mechanisms through which adenosine exerts its effects remain unclear. Although the transfer of regu-latory Th cells blocks colitis induced by pathogenic CD45RB Th cells, we show that CD45RB or CD25 Th cells from AAR-deficient mice do not prevent disease. Moreover, CD45RB Th cells from AAR- deficient mice were not suppressed by control CD45RB Th cells. AAR agonists suppressed the production of proinflammatory cytokines by CD45RB and CD45RB 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 A AR agonist ATL313 attenuated disease in mice receiving CD45RB Th cells. These data suggest that AAR 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. Copyright © 2006 by The American Association of Immunologists, Inc.