Cutting edge: Critical role for A_2A adenosine receptors in the T cell-mediated regulation of colitis

A_2A adenosine receptors (A₂₄AR) 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^high Th cells, we show that CD45RB^low or CD25⁺ Th cells from A_2AAR-deficient mice do not prevent disease. Moreover, CD45RB^high Th cells from A_2AAR- deficient mice were not suppressed by control CD45RB^low Th cells. A₂₄AR agonists suppressed the production of proinflammatory cytokines by CD45RB^high and CD45RB^low 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 ₂₄AR agonist ATL313 attenuated disease in mice receiving CD45RB ^high Th cells. These data suggest that A_2AAR 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.