IP10/CXCL10 - CXCR3 interaction: a potential self-recruiting mechanism for cytotoxic lymphocytes in lichen sclerosus et atrophicus.
Lichen sclerosus et atrophicus is a chronic inflammatory skin disease of unknown aetiology. Recent studies have indicated that autoimmune mechanisms might be involved in its pathogenesis and have suggested a role for autoreactive cytotoxic T-lymphocytes. Based on recent observations we now hypothesize that a type I interferon-driven inflammation might be involved in the pathogenesis of this disease. Lesional skin biopsies were analysed by immunohistochemistry (CD3, CD4, CD8, CD68, CD123, Tia1, Granzyme B, Myxovirus resistance A, IP10/CXCL10 and CXCR3). Sequential double staining was performed to analyse co-expression of Tia1 and CXCR3. Significant expression of Myxovirus resistance A was found, indicating type I interferon production. This expression was closely associated with the expression of the interferon-inducible protein IP10 and the recruitment of CXCR3+ cytotoxic T-lymphocytes. Plasmacytoid dendritic cells appeared to be a major source of type I interferon in lichen sclerosus et atrophicus. Interestingly, several infiltrating lymphocytes contained IP10 in their granules. This is the first study providing evidence that a type I interferon-associated recruitment of CXCR3+ cytotoxic T-lymphocytes is involved in the pathogenesis of lichen sclerosus et atrophicus. Infiltrating lymphocytes, containing IP10 in their granules, could provide an important self-perpetuating mechanism.
Wenzel
Joerg
J
Department of Dermatology, University of Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
Wiechert
Andreas
A
Merkel
Christian
C
Bieber
Thomas
T
Tüting
Thomas
T
D000328:Adult; D000368:Aged; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000276:immunology*; D002648:Child; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D018459:Lichen Sclerosus et Atrophicus / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007370:Interferon Type I; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D019204:GTP-Binding Proteins