Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis.
A(2A) adenosine receptors (A(2A)AR) 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 CD45RB(high) Th cells, we show that CD45RB(low) or CD25+ Th cells from A(2A)AR-deficient mice do not prevent disease. Moreover, CD45RB(high) Th cells from A(2A)AR-deficient mice were not suppressed by control CD45RB(low) Th cells. A(2A)AR 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-beta, were minimally affected. Oral administration of the A(2A)AR agonist ATL313 attenuated disease in mice receiving CD45RB(high) Th cells. These data suggest that A(2A)AR 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.
Naganuma
Makoto
M
Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Wiznerowicz
Elizabeth B
EB
Lappas
Courtney M
CM
Linden
Joel
J
Worthington
Mark T
MT
Ernst
Peter B
PB
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens