Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis.
BACKGROUND
Dermatomyositis (DM) is an autoimmune disease of unknown origin affecting skin and muscles. Infiltrating autoreactive T lymphocytes are thought to play an important pathogenetic role, but it is unclear which mechanisms are involved in the recruitment of these cells. Recent studies provided evidence that a type I interferon (IFN)-driven immune response, including the recruitment of T cells via IP10/CXCR3 interactions, might be important for the generation of skin lesions of cutaneous lupus erythematosus (CLE), an autoimmune disease that shares some clinical and histopathological features with DM. We hypothesized that a similar mechanism might also be involved in the pathogenesis of DM skin lesions.


METHODS
Skin biopsies of 23 donors (11 DM, 5 healthy controls, 7 CLE controls) were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, CD68, CD123, the chemokine receptor CXCR3 and its ligand IP10/CXCL10, and the myxovirus-resistance protein A (MxA)-protein, which is a specific marker for type I IFNs.


RESULTS
We detected strong expression of the MxA protein in all DM skin biopsies, indicating involvement of type I IFNs. Expression of MxA was closely associated with expression of the interferon-inducible protein IP10/CXCL10 and the recruitment of CXCR3+ lymphocytes. Plasmacytoid dendritic cells appear to be an important source of type I IFNs in DM.


CONCLUSIONS
Our results support the hypothesis that lesional type I IFN signalling, induction of IP10 expression, and recruitment of potentially autoreactive T cells via IP10/CXCR3 interaction are involved in the pathogenesis of DM skin lesions.
Wenzel
J
J
Department of Dermatology, University of Bonn, Germany. joerg.wenzel@ukb.uni-bonn.de
Schmidt
R
R
Proelss
J
J
Zahn
S
S
Bieber
T
T
Tüting
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003882:Dermatomyositis / Q000276:immunology* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D008179:Lupus Erythematosus, Discoid / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology*
D015703:Antigens, CD; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007370:Interferon Type I; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D019204:GTP-Binding Proteins