Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by systemic disease flares, renal complications, photosensitivity, and other clinical manifestations. A research area of particular interest to our lab is photosensitivity, an immune system reaction precipitated by ultraviolet radiation (UVR) exposure that results in epidermal keratinocyte apoptosis and contributes to overall skin inflammation. Importantly, many SLE patients attribute a decrease in quality of life due to photosensitivity. Our lab has recently identified a mechanism in which a disintegrin and metalloprotease 17 (ADAM17) located on Langerhans cells (LCs) limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation in mice and humans. While we have delineated the downstream effects of UVR-induced ADAM17 activity and expression in healthy and SLE skin, factors that regulate ADAM17 remain poorly understood. Previous studies have shown that elevated levels of type I interferon (IFN) are characteristic of SLE patients. Here, we hypothesize that type I interferon may regulate ADAM17 in LCs in lupus models.

Methods To quantify ADAM17 activity, we developed an assay that uses flow cytometry and co-culture systems. We use this assay in in vitro models and in vivo mouse models. To quantify the relative ratio of IFN-inducible genes, we use quantitative polymerase chain reaction (qPCR). To apply IFN-k to mice, we solubilize the protein and paint it on murine back skin.

Results In vitro methods showed that type I IFN was sufficient to reduce LC ADAM17 activity, and in vivo models showed that type I IFN receptor blockade corrected the LC ADAM17 defect in photosensitive lupus mouse models. We are analyzing qPCR data.

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Abstract 17 Figure 1

Interferon is a sufficient and necessary condition to downregulate ADAM17 activity

Conclusions We show that type I interferon (IFN) can reduce ADAM17 activity on epidermal cells. We also show that type I interferon receptor blockade in lupus mouse models rescues ADAM17 activity. Our data together suggest that type I IFN in lupus may contribute to Langerhans cell dysfunction and propensity to photosensitivity in SLE.

Funding Source(s): None