Plasmacytoid dendritic cells in multiple sclerosis:: Intracerebral recruitment and impaired maturation in response to interferon-β
Plasmacytoid dendritic cells in multiple sclerosis:: Intracerebral recruitment and impaired maturation in response to interferon-β
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DOI：
10.1097/nen.0b013e31816fc975
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发表时间：
2008-05-01
影响因子：
3.2
通讯作者：
Coccia, Eliana Marina
中科院分区：
文献类型：
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作者：
Lande, Roberto;Gafa, Valerie;Coccia, Eliana Marina
浆细胞样树突状细胞（pDCs）在多发性硬化症（MS）患者中的作用及其对干扰素(IFN)- β治疗的反应尚不清楚。我们在MS脑的白质病变和轻脑膜中发现了pDC的积累，并发现了I型IFN诱导蛋白MxA的丰富表达，主要是在病变的血管周围CD3（+）淋巴细胞中，表明激活的pDCs产生了I型IFN。病变内脑血管内皮细胞检测到pDC趋化剂趋化素，并在包括pDC在内的浸润性白细胞上表达趋化素受体。在ifn - β治疗前和治疗期间评估ifn - β对MS患者pDC表型和功能的影响。虽然ifn - β没有改变循环pDC的频率和不成熟表型，但它们表现出主要组织相容性复合体Class 11和血树突状细胞抗原2分子的表达降低，CD38和B7H1共刺激分子的表达上调。体外暴露于CpG （DNA序列中胞嘧啶[C]位于鸟嘌呤[G]旁边的位置[p表示C和G通过磷酸二酯键连接]）寡脱氧核苷后，ifn - β治疗的MS患者的pDC成熟标记CD83和CD86分子的表达降低；体外对健康供体的pDCs进行ifn - β处理，导致促炎细胞因子（包括ifn - α）的分泌减少，并降低了对成熟刺激刺激同种异体T细胞的能力。这些数据表明，ifn - β调节pDC的免疫功能，从而确定pDC作为ifn - β治疗MS患者的新靶点。
The roles of plasmacytoid dendritic cells (pDCs) and their response to interferon (IFN)-beta therapy in multiple sclerosis (MS) patients are poorly understood. We identified pDC accumulation in white matter lesions and leptomeninges of MS brains and abundant expression of the Type I IFN-induced protein MxA, mainly in perivascular CD3(+) lymphocytes in lesions, indicating Type I IFN production by activated pDCs. The pDC chemoattractant chemerin was detected in intralesional cerebrovascular endothelial cells, and the chemerin receptor was expressed on infiltrating leukocytes, including pDCs. The effect of IFN-beta on pDC phenotype and function was evaluated in MS patients before and during IFN-beta treatment. Although IFN-beta did not modify the frequency and immature phenotype of circulating pDC, they showed lower expression of major histocompatibility complex Class 11 and blood-dendritic cell antigen 2 molecules and upregulation of CD38 and B7H1 costimulatory molecules. On exposure to CpG (a site where cytosine [C] lies next to guanine [G] in the DNA sequence [the p indicates that C and G are connected by a phosphodiester bond]) oligodeoxynuelcotides in vitro, pDCs from IFN-beta-treated MS patients showed reduced expression of the pDC maturation markers CD83 and CD86 molecules; in vitro IFN-beta treatment of pDCs from healthy donors resulted in lower secretion of proinflammatory cytokines, including IFN-alpha, and a decreased ability to stimulate allogencic T cells in response to maturative stimuli. These data indicate that IFN-beta modulates the immunologic functions of pDC, thus identifying pDCs as a novel target of IFN-beta therapy in MS patients.