Prostaglandin E2-mediated T cell suppression requires expression of hydroxyprostaglandin dehydrogenase in regulatory T cells.

Prostaglandins are involved in maintaining tissue integrity under homeostatic conditions. However, in chronic inflammation and cancer prostaglandins have been linked to immune deviation including strong suppression of effector T-cell function. Yet, the molecular mechanisms underlyingimmunosuppression and the cell types involved are only purely understood. Here, we show for the first time that Treg cells are the critical cellular component exerting immunosuppressive effects in prostaglandin E2 (PGE2)-rich environments. Hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes PGE2 into immunosuppressive metabolites, is the critical molecular link between prostaglandin accumulation, increased Treg-cell function and avoidance of tissue destruction. Conditional HPGD knockout mice were crossed to FOXP3-Cre-YFP mice and Treg and Tconv isolated from spleens of these mice were compared with Treg and Tconv cells from control animals.前列腺素（Prostaglandins）在稳态条件下参与维持组织完整性。然而，在慢性炎症与癌症进程中，前列腺素已被证实与免疫偏离密切相关，包括强力抑制效应T细胞（effector T-cell）的功能。但目前针对免疫抑制的分子机制及所涉及的细胞类型，仍未被充分阐明。本研究首次证实，调节性T细胞（Treg cells）是富含前列腺素E2（prostaglandin E2, PGE2）的微环境中发挥免疫抑制作用的关键细胞组分。羟基前列腺素脱氢酶（Hydroxyprostaglandin dehydrogenase, HPGD）可将PGE2代谢为免疫抑制性代谢产物，是连接前列腺素积累、调节性T细胞功能增强与组织损伤规避的关键分子桥梁。我们将条件性HPGD敲除小鼠与FOXP3-Cre-YFP小鼠进行杂交，并从这些小鼠的脾脏中分离得到调节性T细胞与传统T细胞（Tconv），将其与对照组动物来源的对应细胞开展对比分析。