CXCR3-mediated recruitment of cytotoxic lymphocytes in lupus erythematosus profundus.

Background: Lupus erythematosus profundus (LEP) is a rare variant lupus erythematosus with unclear etiology characterized by lobular panniculitis. Recently, we observed a case of LEP involving the lower right eyelid. Our immunohistological analyses of lesional skin biopsies revealed a type I IFN signature in the context of cytotoxic lobular panniculitis.

Objective: Since type I IFNs have been shown to be involved in other cutaneous LE subtypes, especially in chronic discoid LE, we hypothesized that a type I IFN driven immune response might play an important role in the pathogenesis of LEP.

Methods: In addition to the above case, 9 skin biopsies taken from 5 patients with LEP were analyzed for a type I interferon signature by immunohistochemistry. Furthermore, 8 skin biopsies taken from patients with active chronic discoid LE and 5 biopsies of healthy skin were included for control purposes. The inflammatory infiltrate was characterized using monoclonal antibodies specific for CD3, CD4, CD8, CD20, CD68, and CD123. Subsequently, we analyzed the expression the type I IFN Marker MxA, the cytotoxic molecules granzyme B and Tia1, the chemokine receptor CXCR3 and its ligand, the interferon inducible protein IP10/CXCL10.

Results: LEP skin lesions were characterized by a lobular panniculitis, dominated by cytotoxic CXCR3(+) lymphocytes. Strong MxA expression indicated extensive type I IFN production within the fat lobules. Numerous plasmacytoid dendritic cells appear to be the major source of type I IFNs. Lesional expression of IP10 links the type I IFN production and recruitment of CXCR3(+) lymphocytes.

Conclusions: The study was based on histological and immunohistological analyses in a limited number of patients, due to the rareness of the investigated disease. Conclusions: Our results demonstrate a type I IFN driven immune response in active LEP skin lesions. We suggest that this type I IFN driven inflammation is responsible for the recruitment of CXCR3(+) lymphocytes into fat lobules and enhance their cytotoxic capacity.