Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus

被引:187
作者
Wenzel, J
Wörenkämper, E
Freutel, S
Henze, S
Haller, O
Bieber, T
Tüting, T
机构
[1] Univ Bonn, Dept Dermatol, D-53105 Bonn, Germany
[2] Univ Freiburg, Inst Med Microbiol & Hyg, Dept Virol, D-7800 Freiburg, Germany
关键词
cutaneous lupus erythematosus; chemokine; chemokine receptor; skin inflammation;
D O I
10.1002/path.1721
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:435 / 442
页数:8
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