Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-23
pubmed:abstractText
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/CXCL10, 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 rho = 0.56, p < 0.001; dermis: rho = 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3417
pubmed:author
pubmed:issnType
Print
pubmed:volume
205
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
435-42
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15685590-CD8-Positive T-Lymphocytes, pubmed-meshheading:15685590-Cells, Cultured, pubmed-meshheading:15685590-Chemokine CXCL10, pubmed-meshheading:15685590-Chemokines, CXC, pubmed-meshheading:15685590-Female, pubmed-meshheading:15685590-GTP-Binding Proteins, pubmed-meshheading:15685590-Humans, pubmed-meshheading:15685590-Immunity, Cellular, pubmed-meshheading:15685590-Interferon Type I, pubmed-meshheading:15685590-Keratinocytes, pubmed-meshheading:15685590-Lupus Erythematosus, Cutaneous, pubmed-meshheading:15685590-Lupus Erythematosus, Discoid, pubmed-meshheading:15685590-Male, pubmed-meshheading:15685590-Receptors, CXCR3, pubmed-meshheading:15685590-Receptors, Chemokine, pubmed-meshheading:15685590-Signal Transduction, pubmed-meshheading:15685590-Skin, pubmed-meshheading:15685590-Th1 Cells
pubmed:year
2005
pubmed:articleTitle
Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus.
pubmed:affiliation
Department of Dermatology, University of Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
pubmed:publicationType
Journal Article