Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus
Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus
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DOI：
10.1016/j.jaut.2012.07.005
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发表时间：
2013-02-01
影响因子：
12.8
通讯作者：
Schaekel, Knut
中科院分区：
文献类型：
--
作者：
Haensel, Anja;Guenther, Claudia;Schaekel, Knut
红斑狼疮（LE）是一种自身免疫性疾病，有证据表明IL-23和IL-17诱导的免疫病理学。对于支持这种免疫反应的树突状细胞的类型知之甚少。我们最近证明了人6-磺胺LacNAc-树突状细胞（slanDCs）的强Th 1-和Th 17-T细胞诱导能力，并鉴定了slanDCs作为银屑病局部表达IL-23、TNF-α和诱导型一氧化氮合酶（iNOS）的炎性真皮树突状细胞。在这项研究中，我们研究了slanDCs在LE中的作用。使用免疫组化，我们确定slanDCs在皮肤和系统性LE受影响的皮肤病变的频率增加。发现slanDC分散在真皮隔室中，并且也聚集在淋巴滤泡样结构中。在这里，它们与外周的T细胞共定位，但不与中心的B细胞共定位。皮肤slanDC对TNF-α的阳性染色表明其促炎状态。在体外，当在存在来自LE患者的血清的情况下培养slanDCs时，可诱导TNF-α的产生。LE血清的刺激组分先前被鉴定为具有与TLR 7和TLR 8结合的ssRNA的自身免疫复合物。我们发现slanDCs表达TLR 7和TLR 8的mRNA。用ssRNA、选择性TLR 7或TLR 8配体刺激的slanDC响应高水平TNF-α和IL-12产生。与slanDCs相反，CD 1c（+）DCs和浆细胞样DCs（pDCs）表达TLR 7或TLR 8，它们产生TNF-α和IL-12的相应配体远不明显。我们的结论是，slanDCs的分子和功能特征的促炎性髓样DC类型相关的LE的免疫发病机制。皇冠版权所有（C）2012由爱思唯尔有限公司出版。保留所有权利。
Lupus erythematosus (LE) is an autoimmune disease with evidence for an IL-23- and IL-17-induced immunopathology. Little is known about the type of dendritic cells supporting this immune response. We recently demonstrated the strong Th1- and Th17-T-cell inducing capacity of human 6-sulfa LacNAc-dendritic cells (slanDCs), and identified slanDCs as inflammatory dermal dendritic cells in psoriasis locally expressing IL-23, TNF-alpha and inducible nitric oxide synthase (iNOS). In this study, we investigated the role of slanDCs in LE. Using immunohistochemistry, we identified slanDCs at increased frequency in affected skin lesions of cutaneous and systemic LE. slanDCs were found scattered in the dermal compartment and also clustered in lymph follicle-like structures. Here, they colocalized with T cells in the periphery but not with B cells in the center. The positive staining of dermal slanDCs for TNF-alpha indicated their pro-inflammatory status. In vitro the production of TNF-alpha was induced when slanDCs were cultured in the presence of serum from patients with LE. Stimulatory components of LE serum were previously identified as autoimmune complexes with ssRNA binding to TLR7 and TLR8. We found that slanDCs express mRNA for TLR7 and TLR8. slanDCs stimulated with ssRNA, selective TLR7 or TLR8 ligands responded with high-level TNF-alpha and IL-12 production. In contrast to slanDCs, the population of CD1c(+) DCs and plasmacytoid DCs (pDCs) expressed either TLR7 or TLR8, and their production of TNF-alpha and IL-12 to respective ligands was far less pronounced. We conclude that slanDCs have molecular and functional features of a pro-inflammatory myeloid DC type relevant for the immunopathogenesis of LE. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.