Type I interferon-associated cytotoxic inflammation in lichen planus


Joerg Wenzel, MD, Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany
Tel: +49 228 287 5370
Fax: +49 228 287 9000 6969
e-mail: joerg.wenzel@ukb.uni-bonn.de


Introduction:  Lichen planus (LP) is an inflammatory autoimmune skin disease of unknown origin. Evidence has accumulated that autoreactive cytotoxic CD8+ T lymphocytes cause destruction of keratinocytes. Recent studies suggested that type I interferons (IFNs) play a central role in cytotoxic skin inflammation by increasing the expression of IP10/CXCR10 and recruiting effector cells via CXCR3. Here, we investigated whether type I IFNs are also involved in the pathogenesis of LP.

Patients and methods:  Skin biopsies of altogether 17 donors (seven LP and 10 healthy controls) were analyzed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, CD68, CXCR3, granzyme B, IP10/CXCL10, CD123, and the MxA protein, which is specifically induced by type I IFNs.

Results:  Our analysis revealed a significant expression of the MxA protein in all LP skin biopsies, indicating involvement of type I IFNs. Expression of MxA was closely associated with the recruitment of CXCR3+ and granzyme B+ lymphocytes, indicating a Th1-biased cytotoxic immune response. Strong expression of the CXCR3 ligand, the interferon-inducible protein IP10/CXCL10, links type I IFN expression and recruitment of CXCR3+ lymphocytes. Plasmacytoid dendritic cells (pDCs) appear to be a major source of type I IFNs in LP.

Discussion:  Our observations support the hypothesis that lesional type I IFNs produced by pDCs plays an important role in chronic cytotoxic inflammation of LP by recruiting cytotoxic effector lymphocytes via IP10/CXCR3 interactions.