Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus
Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus
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DOI：
10.1002/path.1721
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发表时间：
2005-03-01
影响因子：
7.3
通讯作者：
Tüting, T
中科院分区：
文献类型：
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作者：
Wenzel, J;Wörenkämper, E;Tüting, T
最近的研究表明，I型干扰素（IFN）在红斑狼疮（LE）的发病机制中发挥作用，LE是一种病因不明的自身免疫性疾病。天然产生干扰素的浆细胞样细胞已被证明在皮肤LE（CLE）病变，沿着IFN-α mRNA水平升高。本研究的假设是CLE中I型IFN的局部产生通过诱导IFN诱导型趋化因子如IP 10/CXCL 10诱导Th 1偏向性炎症，导致趋化因子受体CXCR 3表达T细胞募集到皮肤病变中。从21例患有不同类型的活动性皮肤LE的患者的皮肤活检进行了分析MxA的表达，特异性诱导的蛋白质I型干扰素，IFN-诱导蛋白IP 10/CXCLI 0，和趋化因子受体CXCR 3，Th 1细胞的特征，通过免疫组织化学。此外，通过流式细胞术研究外周CD 4+和CD 8 + T细胞的MxA和CXCR 3表达。皮肤LE病变的特征在于MxA的强表达，表明皮肤中局部I型IFN信号传导的诱导。在CLE皮肤病变中检测到大量浸润的CXCR 3阳性淋巴细胞，并且与病变MxA表达密切相关（表皮：斯皮尔曼p = 0.56，p < 0.001;真皮：p = 0.82，p < 0.001）。在患有活动性CLE病变的患者中，循环CD 4+和CD 8 + T细胞的细胞内MxA水平显著增强。表达CXCR 3的外周T细胞百分比在特定CLE亚型中显著降低。IP 10/CXCL 10在表皮中的表达将I型IFN信号传导和CXCR 3 + T细胞的募集联系起来。这些结果表明，I型干扰素信号在皮肤红斑狼疮的发病机制中的重要作用。有人提出，I型IFN诱导Th 1偏向的炎性免疫应答，并将表达CXCR 3的T淋巴细胞募集到皮肤中。版权所有（C）2005大不列颠和爱尔兰病理学会。出版社：John Wiley R Sons，Ltd
Recent studies have suggested that type I interferons (IFN) play a role in the pathogenesis of lupus erythematosus (LE), an autoimmune disease of unknown aetiology. Natural interferon-producing plasmacytoid cells have been demonstrated in cutaneous LE (CLE) lesions, along with elevated levels of IFN-alpha mRNA. The hypothesis in the current study was that local production of type I IFNs in CLE induces Th1-biased inflammation via induction of IFN-inducible chemokines such as IP10/CXCL10 leading to the recruitment of chemokine receptor CXCR3 expressing T-cells into skin lesions. Skin biopsies from 21 patients suffering from different types of active cutaneous LE were analysed for the expression of MxA, a protein specifically induced by type I interferons, the IFN-inducible protein IP10/CXCLI0, and the chemokine receptor CXCR3, characteristic for Th1 cells, by immunohistochemistry. Additionally, peripheral CD4+ and CD8+ T-cells were investigated for the expression of MxA and CXCR3 by flow cytometry. Cutaneous LE lesions were characterized by strong expression of MxA indicating the induction of localized type I IFN signalling in the skin. Large numbers of infiltrating CXCR3 positive lymphocytes were detected in CLE skin lesions, and correlated closely with lesional MxA expression (epidermis: Spearman's p = 0.56, p < 0.001; dermis: p = 0.82, p < 0.001). Intracellular MxA levels of circulating CD4+ and CD8+ T-cells were significantly enhanced in patients with active CLE lesions. The percentage of peripheral T-cells expressing CXCR3 was significantly decreased in specific CLE subtypes. Expression of IP10/CXCL10 in the epidermis links type I IFN signalling and recruitment of CXCR3+ T cells. These results suggest an important role for type I interferon signalling in the pathogenesis of cutaneous lupus erythematosus. It is proposed that type I IFNs induce a Th1-biased inflammatory immune response, with recruitment of CXCR3-expressing T-lymphocytes into the skin. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley R Sons, Ltd.