Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-γ-induced CXCL10 production by immature human dendritic cells
Histamine and prostaglandin E2 up-regulate the production of Th2-attracting chemokines (CCL17 and CCL22) and down-regulate IFN-γ-induced CXCL10 production by immature human dendritic cells
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DOI：
10.1111/j.1365-2567.2006.02326.x
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发表时间：
2006-04-01
期刊：
影响因子：
6.4
通讯作者：
Jeannin, P
中科院分区：
文献类型：
--
作者：
McIlroy, A;Caron, G;Jeannin, P
在靶器官（即皮肤或支气管粘膜）中积累的效应记忆T辅助2（Th 2）细胞在过敏性疾病的发病机制中具有中心作用。迄今为止，选择性触发局部产生Th 2吸引趋化因子的因素仍然知之甚少。在粘膜中，在过敏原进入的部位，未成熟的树突状细胞（DC）与肥大细胞紧密接触。组胺和前列腺素E-2（PGE（2））是由过敏原激活的肥大细胞释放的两种介质，其有利于成熟DC极化为Th 2极化细胞。我们在此分析了组胺和PGE（2）对人DC产生的原型Th 2-（CCL 17，CCL 22）与Th 1-（CXCL 10）趋化因子的影响。我们报道了组胺和PGE（2）剂量依赖性地上调单核细胞来源的未成熟DC的CCL 17和CCL 22。这些作用被肿瘤坏死因子-α增强，在Th 1-细胞因子干扰素-γ（IFN-γ）存在下仍观察到，并被免疫调节细胞因子白细胞介素-10消除。此外，组胺和PGE（2）下调IFN-γ诱导的单核细胞来源的DC产生CXCL 10。组胺和PGE（2）的这些特性在转录水平上观察到，主要通过组胺的H2受体和PGE（2）的EP 2和EP 4受体介导。最后，组胺和PGE（2）也上调CCL 17和CCL 22，并减少IFN-γ诱导的纯化人髓样DC产生CXCL 10。总之，这些数据表明，除了将DC极化为促进幼稚T细胞分化为Th 2细胞的成熟细胞外，组胺和PGE（2）还可作用于未成熟DC，通过选择性控制Th 1/Th 2吸引趋化因子的产生，触发局部Th 2细胞募集，从而有助于维持有利于持续免疫球蛋白E合成的微环境。
Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2-attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E-2 (PGE(2)) are two mediators released by allergen-activated mast cells that favour the polarization of maturing DC into Th2-polarizing cells. We analysed here the effects of histamine and PGE(2) on the prototypic, Th2-(CCL17, CCL22) versus Th1-(CXCL10) chemokine production by human DC. We report that histamine and PGE(2) dose-dependently up-regulate CCL17 and CCL22 by monocyte-derived immature DC. These effects were potentiated by tumour necrosis factor-alpha, still observed in the presence of the Th1-cytokine interferon-gamma (IFN-gamma) and abolished by the immunomodulatory cytokine interleukin-10. In addition, histamine and PGE(2) down-regulated IFN-gamma-induced CXCL10 production by monocyte-derived DC. These properties of histamine and PGE(2) were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE(2). Finally, histamine and PGE(2) also up-regulated CCL17 and CCL22 and decreased IFN-gamma-induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naive T-cell differentiation into Th2 cells, histamine and PGE(2) may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2-attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis.