TY - JOUR
T1 - Cutting edge
T2 - Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis
AU - Naganuma, Makoto
AU - Wiznerowicz, Elizabeth B.
AU - Lappas, Courtney M.
AU - Linden, Joel
AU - Worthington, Mark T.
AU - Ernst, Peter B.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - A2A 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 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. A24AR 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 A 24AR agonist ATL313 attenuated disease in mice receiving CD45RB high 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.
AB - A2A 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 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. A24AR 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 A 24AR agonist ATL313 attenuated disease in mice receiving CD45RB high 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.
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U2 - 10.4049/jimmunol.177.5.2765
DO - 10.4049/jimmunol.177.5.2765
M3 - Article
C2 - 16920910
AN - SCOPUS:33747785278
SN - 0022-1767
VL - 177
SP - 2765
EP - 2769
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -