Reich Kristian, Hugo Sabine, Middel Peter, Blaschke Volker, Heine Andrea, Neumann Christine
Department of Dermatology, Georg-August-University, Göttingen, Germany.
Exp Dermatol. 2004 Dec;13(12):740-7. doi: 10.1111/j.0906-6705.2004.00251.x.
Maturation of dendritic cells (DCs) influences important DC functions such as production of cytokines. Recently, DCs were identified as a source of interleukin-16 (IL-16), a chemotactic factor for DCs themselves, CD4+ T cells, and eosinophils. There is evidence that DC-derived IL-16 may contribute to the pathogenesis of atopic dermatitis (AD).
To investigate the production of IL-16 during differentiation of monocytes into DCs in healthy individuals and patients with AD.
IL-16 production was investigated by quantitative real-time RT-PCR, intracellular cytokine staining, immunoblotting, and ELISA.
DCs generated from peripheral monocytes by 5-day culture in the presence of IL-4 and granulocyte/macrophage colony-stimulating factor acquired the capability to synthesize, store, and secrete IL-16. Storage and release of IL-16 was further enhanced during final DC maturation induced by additional 3-day culture with tumor necrosis factor-alpha (TNF-alpha) and monocyte-conditioned medium. Maturation, as determined by up-regulation of CD83 and CD86 surface expression, and production of IL-16, but not production of IL-10 and IL-12p40 was impaired in day 8 DCs derived from AD patients compared to those from healthy donors. Stimulation of day 8 DCs from AD patients with TNF-alpha and IL-1beta enhanced the expression of CD83 and CD86 and restored the production of IL-16.
Signals involved in the activation and maturation of DCs enhance their capacity to produce IL-16. Functional abnormalities present in patients with AD at the monocyte level may account for impaired maturation and IL-16 production of monocyte-derived DCs.
树突状细胞（DCs）的成熟会影响重要的DC功能，如细胞因子的产生。最近，DCs被确定为白细胞介素-16（IL-16）的来源，IL-16是DCs自身、CD4 + T细胞和嗜酸性粒细胞的趋化因子。有证据表明，DC来源的IL-16可能参与特应性皮炎（AD）的发病机制。
研究健康个体和AD患者单核细胞分化为DCs过程中IL-16的产生情况。
通过定量实时RT-PCR、细胞内细胞因子染色、免疫印迹和ELISA检测IL-16的产生。
在IL-4和粒细胞/巨噬细胞集落刺激因子存在下，外周血单核细胞经5天培养生成的DCs获得了合成、储存和分泌IL-16的能力。在肿瘤坏死因子-α（TNF-α）和单核细胞条件培养基再培养3天诱导DC最终成熟过程中，IL-16的储存和释放进一步增强。与健康供体来源的第8天DCs相比，AD患者来源的第8天DCs中，由CD83和CD86表面表达上调所确定的成熟以及IL-16的产生受损，但IL-10和IL-12p40的产生未受影响。用TNF-α和IL-1β刺激AD患者第8天的DCs可增强CD83和CD86的表达并恢复IL-16的产生。
参与DC激活和成熟的信号增强了其产生IL-16的能力。AD患者在单核细胞水平存在的功能异常可能导致单核细胞来源的DCs成熟和IL-16产生受损。
