Type I interferon-associated cytotoxic inflammation in lichen planus.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Wenzel
Joerg
J
Department of Dermatology, University of Bonn, Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
Scheler
Marina
M
Proelss
Julia
J
Bieber
Thomas
T
Tüting
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007370:Interferon Type I / Q000276:immunology*; D008010:Lichen Planus / Q000276:immunology* / Q000473:pathology; D008297:Male; D018448:Models, Immunological; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; C515187:CXCR3 protein, human; C104577:IP10-Mig receptor; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D053804:Granzymes; D019204:GTP-Binding Proteins