Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept
Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept
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DOI：
10.1111/exd.12190
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发表时间：
2013-08-01
影响因子：
3.6
通讯作者：
Schaekel, Knut
中科院分区：
文献类型：
--
作者：
Guenther, Claudia;Blau, Kristin;Schaekel, Knut
真皮树突状细胞(DC)在银屑病的免疫病理机制中发挥着重要作用。我们以前发现sslanDC是人类血液中产生炎性因子的DC，是银屑病患者真皮中分泌肿瘤坏死因子和CD11c阳性的树突状细胞。在此，我们研究了在依那西普治疗24周期间，肿瘤坏死因子--抑制对10例银屑病患者皮肤和血液中炎性树突状细胞的影响。依那西普治疗降低了真皮SLANDC的频率，但没有诱导细胞凋亡，这是由于缺乏caspase-3的活性表达。同时，我们发现血液中表达较低水平的HLA-DR的slanDC的频率增加。体外刺激健康献血者外周血中分离的sIL-DC可诱导IL-1、IL-6、IL-23和IL-12p70的产生。在依那西普存在的情况下，这种能力被有效地降低，从而表明TNF-是一种自分泌刺激，促进slanDCs的成熟和促炎细胞因子的产生。在体内，我们注意到依那西普的治疗确实减少了真皮sslanDCs的数量，与总的TNF-和IL-23p19的表达平行。然而，成功的治疗并没有下调真皮slanDCs对肿瘤坏死因子-和IL-23p19的阳性表达，表明剩余的slanDC保持其促炎能力。本研究为依那西普在体内皮肤、血液和体外炎症树突状细胞水平上的免疫调节特性提供了新的见解。
Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro-inflammatory TNF-, IL-23- and IL-12-producing DCs in human blood and as prominent inflammatory dermal TNF-secreting and CD11c-positive DC subset in psoriasis. Here, we ask for the effects of TNF--inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase-3-expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA-DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL-1, IL-6, IL-23 and IL-12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF- is an autocrine stimulus for maturation and pro-inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF- and IL-23p19. However, successful treatment did not down-regulated the percentage of dermal slanDCs that stained positive for TNF- and IL-23p19 indicating that remaining slanDCs kept their pro-inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.