Prednisolone suppresses the function and promotes apoptosis of plasmacytoid dendritic cells
Prednisolone suppresses the function and promotes apoptosis of plasmacytoid dendritic cells
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DOI：
10.1111/j.1600-6143.2006.01476.x
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发表时间：
2006-10-01
影响因子：
8.8
通讯作者：
Kwekkeboom, J.
中科院分区：
文献类型：
--
作者：
Boor, P. P. C.;Metselaar, H. J.;Kwekkeboom, J.
器官移植受者在移植后早期对病毒感染高度敏感。浆细胞样树突状细胞（PDC）在抗病毒免疫中发挥重要作用。因此，我们测定了肝移植（LTX）后循环PDC的数量，并确定了免疫抑制剂对PDC存活和功能的影响。对13例接受泼尼松联合环孢素或他克莫司治疗的LTX患者进行纵向PDC测定。纯化的PDC在有或没有临床相关浓度的环孢菌素、他克莫司或泼尼松龙的情况下培养。通过测定活性caspase-3、核凝聚和annexin-V/7AAD染色来监测凋亡诱导。LTX后，观察到循环PDC数量减少4倍（p < 0.01），在泼尼松治疗停止后部分恢复。在体外，泼尼松龙诱导PDC细胞凋亡，而环孢素和他克莫司没有。在Toll样受体（TLR）刺激的PDC中，需要更高剂量的泼尼松龙来诱导凋亡。然而，非凋亡诱导浓度的泼尼松龙抑制干扰素-α的产生，共刺激分子的上调和TLR刺激的PDC的同种异体刺激能力。总之，泼尼松龙诱导PDC细胞凋亡，这解释了移植后循环PDC数量的下降。此外，泼尼松龙抑制TLR刺激的PDC的功能。因此，无皮质类固醇的免疫抑制治疗可能会减少移植后病毒感染的数量和严重程度。
Organ transplant recipients are highly susceptible to viral infections early after transplantation. Plasmacytoid dendritic cells (PDC) play a major role in antiviral immunity. Therefore, we determined the numbers of circulating PDC after liver transplantation (LTX) and established the effects of immunosuppressive drugs on PDC survival and function. PDC were determined longitudinally in 13 LTX recipients treated with prednisone and cyclosporin or tacrolimus. Purified PDC were cultured with or without clinically relevant concentrations of cyclosporin, tacrolimus or prednisolone. Apoptosis induction was monitored by determination of active caspase-3, nuclear condensation and annexin-V/7AAD staining. After LTX, a 4-fold reduction in the number of circulating PDC was observed (p < 0.01), which recovered partially after discontinuation of prednisone treatment. In vitro, prednisolone induced apoptosis in PDC, while cyclosporin and tacrolimus did not. Higher doses of prednisolone were needed to induce apoptosis in Toll-like receptor (TLR)-stimulated PDC. However, non-apoptosis inducing concentrations of prednisolone suppressed interferon-alpha production, upregulation of co-stimulatory molecules and allo-stimulatory capacity of TLR-stimulated PDC. In conclusion, prednisolone induces apoptosis in PDC, which explains the decline in circulating PDC numbers after transplantation. Moreover, prednisolone suppresses the functions of TLR-stimulated PDC. Therefore, corticosteroid-free immunosuppressive therapy may reduce the number and severity of viral infections after transplantation.