LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+T cells through a COX-2-PGE2-dependent mechanism
LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+T cells through a COX-2-PGE2-dependent mechanism
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DOI：
10.1093/intimm/dxm134
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Tasken, Kjetil
中科院分区：
文献类型：
--
作者：
Bryn, Tone;Yaqub, Sheraz;Tasken, Kjetil
单核细胞启动先天性免疫应答，并与T细胞相互作用，通过抗原呈递和分泌体液因子诱导抗原特异性免疫应答。我们先前已经证明适应性调节性T细胞以环氧合酶（考克斯）-2-前列腺素E-2（PGE（2））依赖性方式抑制T细胞效应器功能，并且PGE（2）将静息的CD 4 + CD 25-T细胞转化为具有抑制性表型的FOXP 3 + T细胞。在这里，我们证明了LPS刺激单核细胞通过考克斯-2-PGE（2）依赖性机制导致T细胞免疫应答的抑制，该机制可被考克斯-2抑制剂以及PGE（2）中和抗体和cAMP拮抗剂逆转。此外，我们发现LPS激活的单核细胞通过相同的途径诱导静息CD4 + CD25-T细胞中FOXP3的表达。这些结果表明，单核细胞能够有效地抑制T细胞免疫反应的调节方式，并引发抑制性免疫概况。
Monocytes initiate innate immune responses and interact with T cells to induce antigen-specific immune responses by antigen presentation and secretion of humoral factors. We have previously shown that adaptive regulatory T cells inhibit T-cell effector functions in a cyclooxygenase (COX)-2-prostaglandin E-2 (PGE(2))-dependent manner and that PGE(2) converts resting CD4+CD25- T cells into FOXP3+ T cells with a suppressive phenotype. Here, we demonstrate that stimulation of monocytes with LPS leads to suppression of T-cell immune responses by a COX-2-PGE(2)-dependent mechanism that is reversible with COX-2 inhibitors as well as PGE(2)-neutralizing antibody and cAMP antagonist. Furthermore, we show that LPS-activated monocytes induce FOXP3 expression in resting CD4+CD25- T cells by the same pathway. These results suggest that monocytes are able to efficiently suppress T-cell immune responses in a regulatory manner and elicit an inhibitory immune profile.