Langerhans Cell regulation in human SLE

Lupus is a chronic, systemic autoimmune disease characterized by destructive inflammation of multiple organ systems most commonly the skin, kidneys, joints, and brain. One of the features of lupus is that patients are photosensitive, developing inflammatory skin lesions even with ambient sunlight exposure. Photosensitivity is a major contributor to morbidity, contributing to skin pathology, associated flares of systemic disease, as well as secondary effects such as depression stemming from lifestyle modifications to avoid the sun, and yet treatment options are limited. Langerhans cells are a unique population of immune cells in the epidermis of the skin that limit sun-induced skin inflammation, but they appear to be dysfunctional in lupus, and this dysfunction contributes to photosensitivity. In this study, our goal is to better understand what causes Langerhans cell dysfunction in lupus photosensitivity in order to improve treatment and quality of life for lupus patients. Among the multitude of mediators that are dysregulated in lupus patients, elevated interferon type I represents a key factor driving pathology. Type I interferon is known to be upregulated in lupus skin and recent clinical trials blocking type I interferon activity with anifrolumab in lupus patients have shown beneficial effects, especially in skin. How exactly interferon contributes to skin disease in lupus is not yet well understood, and, here, we will examine the extent to which type I interferon signaling among other molecules contributes to Langerhans cell dysfunction in lupus. We will test the effect of interferon and other molecules found in lupus skin on Langerhans cells and examine for a role of these molecules in Langerhans cell dysfunction in lupus. This study will provide insight into the factors in lupus skin that contribute to Langerhans cell dysfunction and help us better understand mechanisms of lupus skin disease, paving the way to more specific targeted treatment and quality of life for lupus patients.