The ummunobiology of IL 12 receptors expressed on human dendritic cells

树突状细胞（DC）对炎性CC趋化因子的反应性在其成熟过程中下调。我们分析了这些事件背后的机制。CC趋化因子受体（CCR）-1、-3和-5的细胞表面表达在未成熟DC（iDC）从单核细胞分化期间增加。相反，这些表达在iDC发育成成熟DC（mDC）期间降低至与单核细胞的水平相似的水平。CCR-1、CCR-3和CCR =5的转录表达在iDC从单核细胞分化的过程中增加，而在iDC向mDC发育的过程中表达降低。在mDC中检测到CCR-7转录本的表达，但在单核细胞或iDC中未检测到CCR-7转录本的表达。单核细胞和iDC，而不是mDC，响应于炎性CC趋化因子如活化调节正常T细胞表达和分泌的（RANTES）/CCL 5而迁移，而mDC，而不是单核细胞或iDC，迁移到巨噬细胞炎性蛋白（MIP）-3ss/CCL19。RANTES（CCR-1、CCR-3和CCR-5）与单核细胞或iDC的受体结合导致蛋白酪氨酸磷酸化事件，包括粘着斑激酶和促分裂原活化蛋白激酶的活化，而与单核细胞或iDC相比，这种刺激几乎不诱导mDC中这些分子事件的活化。另一方面，用MIP-3 β（CCR-7）刺激诱导mDC中的酪氨酸磷酸化事件，但不在单核细胞或iDC中。这些结果表明，下调CCR的细胞表面表达和下游信号事件可能参与减少趋化性的DC炎性CC趋化因子在其成熟。

Responsiveness of dendritic cells (DC) to inflammatory CC chemokines is down-regulated during their maturation. We analyzed the mechanism underlying these events. Cell-surface expression of CC chemokine receptor (CCR)-1, -3 and -5 was increased during differentiation of immature DC (iDC) from monocytes. In contrast, these expressions were decreased during development of iDC into mature DC (mDC) to levels similar to those of monocytes. Transcriptional expression of CCR-1, -3 and =5 was increased during differentiation of iDC from monocytes, while the expression was decreased during development of iDC into mDC. Expression of CCR-7 transcript was detected in mDC, but not in monocytes or iDC. Both monocytes and iDC, but not mDC, migrated in response to inflammatory CC chemokines such as regulated on activation normal T cell expressed and secreted (RANTES)/CCL5, whereas mDC, but not monocytes or iDC, migrated to macrophage inflammatory protein (MIP)-3ss/CCL19. Receptor engagement of monocytes or iDC by RANTES (for CCR-1, -3 and -5) resulted in protein tyrosine phosphorylation events including activation of focal adhesion kinase as well as mitogen-activated protein kinase, whereas this stimulation induced little activation of these molecular events in mDC when compared with monocytes or iDC. On the other hand, stimulation with MIP-3ss (for CCR-7) induced tyrosine phosphorylation events in mDC, but not in monocytes or iDC. These results suggest that the down-regulation of cell-surface expression of CCR and of their downstream signaling events may be involved in the reduced chemotaxis of DC to inflammatory CC chemokines during their maturation.