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The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets

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Abstract:

Summary Background 

Plasmacytoid dendritic cells and type I interferons (IFNs) are supposed to play a central proinflammatory role in the pathogenesis of cutaneous lupus erythematosus (LE). The IFN-inducible chemokines CXCL9 and CXCL10 are involved in recruiting CXCR3+ effector lymphocytes from the peripheral blood into skin lesions of LE. We hypothesized that the expression pattern of IFN-inducible proteins reflects the characteristic distribution of the inflammatory infiltrate in different subsets of cutaneous LE. Objectives 

To test this hypothesis in patients with LE. Methods 

Lesional skin biopsies taken from patients with different subsets of LE [chronic discoid LE (CDLE), n =12; subacute cutaneous LE (SCLE), n =5; LE tumidus (LET), n =4; LE profundus (LEP), n =6] were investigated by immunohistochemistry using monoclonal antibodies to the lymphocyte surface markers CD3, CD4, CD8, CD20 and CD68, the cytotoxic proteins Tia1 and granzyme B, the chemokine receptor CXCR3, the specifically type I IFN-inducible protein myxovirus protein A (MxA) and the chemokines CXCL9 and CXCL10. Results 

The expression pattern of MxA followed the distribution of the inflammatory infiltrate typically seen in the investigated cutaneous LE subsets. In CDLE and SCLE, expression was focused in the epidermis and upper dermis, while in LET a perivascular and in LEP a subcutaneous pattern was found. Similar findings were obtained for CXCL9 and CXCL10. Conclusions 

Our results demonstrate a close morphological association between the expression pattern of IFN-inducible proteins and the distribution of CXCR3+ CD3+ lymphocytes in all investigated subsets of cutaneous LE. This supports the importance of an IFN-driven inflammation in this condition. Infiltrating lymphocytes carrying CXCL10 in their granules might amplify the lesional inflammation and be responsible for the chronic course of this disease.

Keywords: CXCL10; CXCL9; CXCR3; T cell; cutaneous lupus erythematosus; interferon

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1365-2133.2007.08137.x

Publication date: 2007-10-01

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