Prostaglandin D2 suppresses human NK cell function via signaling through D prostanoid human receptor
Prostaglandin D2 suppresses human NK cell function via signaling through D prostanoid human receptor
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DOI：
10.4049/jimmunol.179.5.2766
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Campbell, Kerry S.
中科院分区：
文献类型：
--
作者：
Chen, Yingying;Perussia, Bice;Campbell, Kerry S.
NK细胞通过产生1型细胞因子和细胞毒性应答在针对肿瘤或病毒感染的免疫应答中发挥关键作用。相反，在2型显性免疫应答期间，例如过敏性疾病，NK细胞的活性通常受损。据报道，这些2型免疫介导的疾病与PGD的局部产生密切相关（2）。PGD（2）是一种主要由肥大细胞和肺泡巨噬细胞合成的类二十烷酸，通过Th 2细胞上的两种主要受体D前列腺素受体（DP）和趋化受体样分子发挥作用。在免疫系统中，PGD（2）与DP结合通常会抑制细胞功能。在本研究中，我们发现：1）通过mRNA分析和Western blot检测到DP在人NK细胞中表达; 2）PGD（2）通过DP信号传导抑制人NK细胞的细胞毒性、趋化性和1型细胞因子的产生; 3）PGD（2）通过DP信号传导升高细胞内cAMP水平，并且对NK细胞的抑制作用是cAMP依赖性的; 4）PGD（2）与DP的结合抑制由活化受体CD 16的交联引发的Ca 2+动员。总之，这些数据揭示了PGD（2）通过DP发挥作用以抑制人NK细胞的1型和细胞溶解功能的新机制，从而有助于促进2型免疫应答。
NK cells play critical roles in immune responses against tumors or virus infections by generating type 1 cytokine and cytotoxicity responses. In contrast, during type 2 dominant immune responses, such as allergic diseases, activities of NK cells are often impaired. These type 2 immune-mediated diseases have been reported to be closely associated with local production of PGD(2). PGD(2) is an eicosanoid primarily synthesized by mast cells and alveolar macrophages, and it functions through two major receptors, D prostanoid receptor (DP) and chemoattractant receptor-like molecule on the Th2 cell. Within the immune system, PGD(2) binding to DP generally leads to suppression of cellular functions. In the current study, we show that: 1) DP is expressed in human NK cells as detected by mRNA analysis and Western blot; 2) PGD(2) inhibits cytotoxicity, chemotaxis, and type 1 cytokine production of human NK cells via signaling through DP; 3) PGD(2) signaling via DP elevates intracellular cAMP levels and the inhibitory effects on NK cells are cAMP dependent; 4) PGD(2) binding to DP suppresses Ca2+ mobilization triggered by the cross-linking of the activating receptor, CD16. Together, these data uncover a novel mechanism by which PGD(2) functions through DP to suppress type 1 and cytolytic functions of human NK cells, thus contributing to the promotion of a type 2 immune response.