Cutting edge:: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis
Cutting edge:: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis
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DOI：
10.4049/jimmunol.177.5.2765
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发表时间：
2006-09-01
影响因子：
4.4
通讯作者：
Ernst, Peter B.
中科院分区：
文献类型：
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作者：
Naganuma, Makoto;Wiznerowicz, Elizabeth B.;Ernst, Peter B.
A(2A)腺苷受体(A(2A)A-R)抑制炎症，尽管腺苷发挥作用的机制尚不清楚。尽管调节性A细胞的转移阻止了致病的CD45Rb(高)Th细胞引起的结肠炎，但我们发现来自A(2A)AR缺陷小鼠的CD45Rb(低)或CD25(+)Th细胞并不能预防疾病。此外，来自A(2A)AR缺陷小鼠的CD45Rb(高)Th细胞不受对照CD45Rb(低)Th细胞的抑制。A(2A)受体激动剂抑制CD45RB(高)和CD45RB(低)T细胞产生促炎细胞因子，并导致mRNA稳定性丧失。相比之下，抗炎细胞因子，包括IL-10和转化生长因子-B，受到的影响最小。口服A(2A)AR激动剂ATL313可减轻接受CD45RB(高)A细胞的小鼠的疾病。这些数据表明，A(2A)AR通过抑制促炎细胞因子的表达，同时抑制IL-10和TGF-P介导的抗炎活性，在控制T细胞介导的结肠炎方面发挥了新的作用。
A(2A) adenosine receptors (A(2A)A-R) inhibit inflammation, although the mechanisms through which adenosine exerts its effects remain unclear. Although the transfer of regulatory A 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-B, were minimally affected. Oral administration of the A(2A)AR agonist ATL313 attenuated disease in mice receiving CD45RB(high) A 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-P.